what is diabetes mellitus various types physiology

1. Diabetes mellitus and periodontal diseases
PRESENTED
BY
PUNIT (I YEAR PG)

2. Contents
INTRODUCTION
CLASSIFICATION
METABOLIC ROLE OF INSULIN
TYPE 1- DIABETES
TYPE-2 DIABETES
CLINICAL PRESENTATION OF DIABETES
DIAGNOSIS OF DIABETES
COMPLICATIONS OF DIABETES
PATHOGENESIS OF COMPLICATIONS OF DIABETES
ORAL MANIFESTATIONS OF DIABETES
DIABETES & PERIODONTAL DISEASE
DENTAL MANAGEMENT OF DIABETES
CONCLUSION

3. ...and the Latin word mellitus =
sweet as honey
Diabetes has been recognised since ancient times. It is known by the increased
thirst and frequent urination experienced by the person with diabetes. Often,
this person also feels a generalised weakness.
Later in 1679 the discovery that the urine of a diabetic person had
a sweet taste, gave the condition its name.
The Greek word Diabetes = to Siphon
/pass through

4. Definitions:-
Gaw et al(1955)-defined as syndrome characterized by hyperglycemia due to
an absolute or relative risk of insulin or insulin resistance.
Maline(1968)- defined as chronic disorder of carbohydrate metabolism
characterized by hyperglycemia and glycosuria.
National diabetes data group(1979) defined diabetes mellitus as a genetically and
clinically heterogenous group of disorders that shared glucose intolerance in
common.

5. Ervasti et al (1985)-defined diabetes mellitus as a metabolic disorder with disturbances in the intrinsic production, of
insulin leading to an abnormal fat , carbohydrate and protein metabolism .
Bennet (1994)- defined as a syndrome characterized by hyperglycemia and disturbances of carbohydrate, fat and
protein metabolism associated with absolute or relative deficiencies in insulin action and secretion.
Presently it is defined as a complex metabolic disease ,characterized by hyperglycemia , diminished insulin production
,impaired insulin action or a combination of both ,which results in the inability of glucose to be transported from blood
stream into the tissues ,which in turn results in high blood glucose levels and excretion of sugar in urine .

6. Epidemiology
 Has reached epidemic population worldwide
 150 million cases in 2000
 221 million expected in 2010
 90% are type 2 & it parallels the increase in the incidence of obesity
 Prevalence is similar but slightly greater in men of >60 yrs

7. Classification
 Rifkin and Ross (1975)and Nakkey and Halck (1976)
1) Heriditary / primary
a) potential diabetes
b) sub clinical diabetes
c) latent diabetes
2) Non hereditary / secondary
a) damage or Removal of pancreatic islet tissue
b) disorders of other endocrine glands

8. EDWARD C.M et al (1995)
1) Primary
TYPE I-IDDM
TYPE II-NIDD
2) Secondary
a) Pancreatic pathology
b) Excessive endogenous production of hormonal antagonists to insulin
Growth hormone
Glucocorticoids
Thyroid hormones
c) Medication with corticosteroids , thiazide
3) Associated with genetic syndromes

9. American Diabetes Association Classification of Diabetes Mellitus(1998)
1.Type1(β-cell destruction leads to insulin deficiency)
immune-mediated
idiopathic
2. Type2 (insulin resistance /with relative insulin
deficiency)
3. Gestational diabetes
4.Genetic Defects
Maturity-onset diabetes of young (MODY)

10. 5. Exocrine pancreatic defects
chronic pancreatitis, pancreatectomy, neoplasia, cystic fibrosis ,hemachromatosis
6.Endocrine pancreatic defects
acromegaly ,cushing syndrome, hyperthyroidism, pheochromocytoma, glucagonoma
7.Infections
cytomegalovirus, coxsackie virus B

11. 8.Drugs
glucocorticoids,
thyroid hormone,
thiazides,
nicotinic acid,
phenytoin.
9.Genetic syndrome associated with diabetes
down syndrome,
kleinfelter syndrome,
turner syndrome

12. .

13. Gestational diabetes
Gestational diabetes also involves a combination of inadequate insulin secretion
and responsiveness, resembling type 2 diabetes in several respects. It develops
during pregnancy and may improve or disappear after delivery. Even though it
may be transient, gestational diabetes may damage the health of the fetus or
mother, and about 20%–50% of women with gestational diabetes develop type 2
diabetes later in life.

14. NORMAL ENDOCRINE PANCREAS
The endocrine pancreas consists of about 1million microscopic clusters of cells, the
islets of Langerhans.
The first evidence of islet formation in the human fetus is seen at 9 to 11 weeks.
In aggregate, the islets in the adult human weigh only 1 to 1.5 gm, individually, most
islets measure 100 to 200 m and consists of four major and two minor cell types.

15. The four major types are , ,  and PP (pancreatic polypeptide) cells and the two minor types are D1 and
enterochromaffin cells.
The major types make up about 68%, 20%, 10% and 2% respectively, of the adult islet cell population. They can be
differentiated morphologically by their staining properties, by the ultra structural characteristics of their granules, and by
their hormone content.
The  cell produces insulin, The insulin – containing intracellular granules contain a crystalline matrix with a
rectangular profile, surrounded by a halo.
The  cell produces Glucagon and the granules are found with closely applied membranes and dense center

16.  cells contain Somatostatin, which suppresses both insulin and glucagon release ; they have large, pale
granules with closely applied membranes.
PP cells contain a unique pancreatic polypeptide that exerts a number of gastrointestinal effects, such as
stimulation of secretion of gastric and intestinal enzymes and inhibition of intestinal motility. These cells have
small, dark granules and not only are present in islets, but also are scattered in the exocrine pancreas.
The minor cell type D1 cell elaborate vasoactive intestinal polypeptide (VIP), a hormone that induces
glycogenolysis and hyperglycemia ; it also stimulates gastrointestinal fluid secretion and causes secretory
diarrhoea and Enterochromaffin cells synthesize serotonin and are the source of pancreatic tumors that
causes the carcinoid syndrome.

18. Pancreas

19. Normal glucose metabolism
It is regulated by homeostatic mechanism & maintained within a range of
3.5-6.5 mmol/l.
A balance is maintained between the entry & uptake of glucose.
When intestinal glucose absorption declines, hepatic glucose output is
increased by counter-regulatory hormones, glucogen &adrenaline.
Insulin is secreted from pancreatic beta cells into circulation with in response
to rised blood glucose.

20. Hormone control of glycemia
 Hormones that raise blood glucose
glucogon, catecholamines(epinephrine), growth hormone, thyroid hormone, glucocorticoid
 Hormones that lowers glucose
Insulin

21. Insulin biosynthesis
SYN IN
RER
GOLGI
APP
PLASMA
MEMB
CAPREACHES
BLOOD
TRANSPORTED
MICROTUBULES
EXOCYTOSIS
FENESTRATION

22. PRE PRO
INSULIN
PRO INSULIN
INSULIN
C PEPTIDE
DI SULPHIDE
BONDS

23. MECHANISM OF ACTION
INSULIN RECEPTORS
TWO ά TWO ß
EXTRACELLULAR SPANS THE MEMB
TYROSINE KINASE
ACTIVITY

24. METABOLIC ROLE OF INSULIN
A) Action on carbohydrate metabolism :
Net effect is
Lowering of blood glucose and increase glycogen store.
The above is achieved by several mechanisms :
Increased glucose uptake
Increases glycolysis
Stimulates glycogenesis
Decreases gluconeogenesis
Decreases glycogenolysis
Increasing HMP shunt

26. Insulin facilitates entry of glucose in to muscle, adipose and several other tissues.
The only mechanism by which can cells take up glucose is by facilitated diffusion
through a family of hexose transporters.
The major transporter used for up take of glucose is made by GLUT(glucose T-
transport) which is available in plasma membrane .

27. GLUCOSE TRANSPORTERS
Facilitated diffusion cells
Secondary active transport with Na
Glucose transporters [GLUT1-7]
GLUT 4 Muscle & adipose tissues

28. B) Action on lipid metabolism :
net effects are lowering of FFA , increasing TG store.
The above is achieved by several mechanisms:
Decreases lipolysis
Increases fatty acid synthesis
Increases synthesis of triglycerides
Decreases ketogenesis.
C) Action on protein metabolism :
increases aminoacid transport
increases protine synthesis.

29. d) Action on growth & cell replication :
 Insulin stimulates growth in vivo & also cell proliferation in vitro.
 It has been found that insulin potentiates the ability of :
fibroblast growth factor (FGF)
platelet derived growth factor (PDGF)
epidermal growth factor (EGF)

30. NORMALLY IN THE BODY

31. TYPE 1- DIABETEs (formerly known as insulin dependent
diabetes)
 Type1 diabetes is caused by cell mediated autoimmune destruction of
insulin producing Beta cells in the pancreas .
 ETIOLOGY:
Genetics :
most interest has focused on human leucocyte antigen (HLA)
with in the major histocompatiability complex on short arm of
chromosome 6.
2) Environmental factors:
a) virus
b) diet
c) stress

33. Pathway type 1 Diabetes

35. TYPE2 DIABETES (formerly known as non-insulin dependent
diabetes)
 Commonly occurs in subjects who are obese, insulin
resistant & accompanied by impaired beta cell function.
 ETILOGY
1)GENETICS: Molecular genetics has allowed the
identification of certain specific,& clinically identifiable
forms of type2, which are the results of single gene defects.

37.  However, these subtype such as syndrome of maturity onset diabetes of young
(MODY) are uncommon & constitute 5% of type2.
 MODY are usualy occurs before age 25, & with lack of insulin resistance.
2)ENVIRONMENTAL FACTORS
life style- over eating, obesity, under activity
3)AGE
PATHOGENESIS OF TYPE2 DIABETES:
 Two metabolic defects that characterize type2 diabetes are:
1)Decresed ability of peripheral tissues to respond to insulin (insulin resistance)
2)β-cell dysfunction that is manifested as inadequate insulin secretion in the face of
insulin resistance &hyperglycemia.

39. DIABETES TYPE 2: INSULIN RESISTANCE

40. A) INSULIN RESISTANCE
 Insulin resistance is defined as resistance to the effects of glucose uptake, metabolism,&
storage.
 Studies have shown numerous quantitave& qualitative defects they are:
Abnormalities of insulin signaling pathway.
Down regulation of insulin receptor .
Decresed insulin phoshorylation& tyrosine kinase activity.
Reduced levels of active intermediates in the insulin
signaling pathway.
Fusion of GLUT-4containg vesicles with the plasma membrane.
Impairement of translocation.

41. Obesity & insulin resistance
 The risk for diabetes increases as the body mass index (a measure of
body fat content) increases. It is not only the absolute amount but
also the distribution of body fat that has an effect on insulin
sensitivity .
 Central obesity (abdominal fat) is more likely to be linked with
insulin resistance than are peripheral (gluteal / subcutaneous) fat
depots.

42. β-cell dysfunction
β-cell dysfunction in type2 diabetes manifests as both in qualitative&
quantitative.
Qualitative beta cell dysfunction is initially seen as loss of normal pulsatile,
oscillating pattern of insulin secretion.
Followed by rapid phase of insulin secretion which is triggered by an elevation
in plasma glucose.
Quantitative beta cell dysfunction is reflected by an beta cell mass, islet
degeneration, & deposition of amyloid.

44. CLINICAL PRESENTATION OF DIABETES
characteristics type 1 type 2
1)Age of onset Less than 40 yrs More than 50 yrs
2)Body type Thin or normal Obese
3)Family history Common More common
4)Rapidity of clinical
onset
Abrupt Slow
5)Pathogenesis Autoimmune beta cell
destruction
Insulin resistance ,
impaired insulin secretion
6)Endogenous insulin
production
None Decreased, normal or
elevated.
7)Succeptiability to
ketoacidosis
high low

45. DIAGNOSIS OF DIABETES
 Primary methods used to diagnose diabetes are :
1. Fasting blood glucose,
2. Random plasma glucose,
3. Oral glucose tolerance.

47.  The fasting and casual plasma glucose test and oral glucose tolerance test allow
determination of glycemia at the moment in time when blood sample is draw
 They do not allow evaluation of glycemic control over a more extended time
period.
 The primary test used for this purpose is glycosylated hemoglobin assay .
 Two different glycosylated hemoglobin tests are available :
1)Hb A 1
2)Hb A1 C
 Normal Hb A1 is less than 8% and Hb A1C is less than 6-6.5%.

48. the ADA recommends that diabetic patients try to achieve
target HbA1c of less than 7%, an HbA1c greater than 8%
suggests that alteration in patient management is needed to
improve glucemic control.

49. Self blood glucose monitoring
(SBGM)
has allowed the diabetic pt to rapidly
asses his or her own blood glucose
levels.
Glucometer

51. COMPLICATIONS OF DIABETES
 Acute complications:
Hypoglycemia
Diabetic ketoacidosis
Non ketotic hyperosmolar diabetic coma
 Late complications :
Retinopathy - blindness
Nephropathy – renal failure
Neuropathy – sensory , autonomic
Macro vascular disease - atherosclerosis, stroke
Altered wound healing
Diabetic foot and ulcers

52. Complications- chronic

53. Pathogenesis of complications of diabetes
 At least 3 metabolic pathways appear to be involved in
pathogenesis of long term diabetic complication
 Formation of advanced glycation end products .
 Activation of proteinkinase C
 Intracellular hyperglycemia with disturbances in polyol
pathways.

54. FORMATION OF ADVANCED GLYCATION END PRODUCTS
NON ENZYMATIC RELATIONS
intracellular glucose derived dicarbonyl
precursors (glyoxal,methylglyoxal)
+
Amino group of both intracellular &
extracellular protein
AGEs
Extracellular matrix
components

55. TYPE IV COLLAGEN IN BASEMENT MEMBRANE
AGE TRAPS PROTEIN LIKE LDL
BIOLOGIC EFFECTS OF AGE
Endothelial
adhesion
Fluid filtration
Cholesterol
deposition
atherogenesis

56. ACTIVATION OF PROTEIN KINASE C
Ca
intracellular protein kinase
DAC
diacyl glycerol
Production of the proangiogenic molecule vascular endothelial growth factor
(VEGF), implicated in the neovascularization characterizing diabetic retinopathy.
Increased activity of he vasoconstrictor endothelin – 1 and decreased activity of the
vasodilator endothelial nitric oxide synthase (eNOS) .
HYPERGLYCEMIA

57. Intracellular hyperglycemia with disturbances in polyol
pathways.
In some tissues that do not require insulin for glucose transport (nerves, lenses,
kindneys, blood vessels), hyperglycemia leads to an increase in intracellular
glucose that is then metabolised by the enzyme aldose reductase to sorbitol then
to fructose .

58. In this process, intracellular NADPH is used as a cofactor .NADPH is also required as a
coafactor by the enzyme glutathione reductase for regenerating GSH.
In the face of sustained hyperglycemia , depletion of intracellular NADPH by aldose reductase
leads to compromise GSH regeneration thus causing increased cellular susceptibility to oxidative
stress.

59. KETOSIS
acetoacetyl CoA
 Excess acetyl – CoA
acetone
acetoacetate
beta hydroxy
butyrate
In fasting ketone bodies are source of energy .but in diabetes it piles up in the blood stream due to
much production.

60. ACIDOSIS
 Acetoacetate ,betahydroxybutyrate are anions of the fairly strong acetoacetic acid
&beta hydroxybutyric acid.
ACIDOSIS KUSSMAUL BREATHING
Na & K are lost in urine to compensate
Excessive loss
Dehydration
Hypovolemia
Hypotension
Diabetic coma

61. ACUTE COMPLICATION – DIABETIC KETOACIDOSIS
SIGNS , SYMPTOMS & LABORATORY FINDINGS
Nausea and vomiting
Abdominal pain
Dehydration
dry mucous membranes
tachycardia
hypotension
abnormal skin turgor
Kussmaul’s respiration
Altered mental state
Possible coma
Hyperglycemia
Increased blood urea nitrogen(BUN) & serum creatinine
Decreased serum potassium and phosphorous
Acidosis (arterial pH < 7.3)

62. STUDIES
1. THE DIABETES CONTROL & COMPLICATIONS TRIAL
1400 individuals with type I
conclusion-if all complications of DM were combined individuals in the
intensive diabetes management group would experience 15.3 more yrs of life
without significant microvascular and neurologic complications of DM .
2 UNITED KINGDOM PROSPECTIVE DIABETES STUDY
>5000 individuals with type II
conclusion-there was a continuous relationship b/w glycemic control &
development of complications.

63. DIABETIC RETINOPATHY
 Intra retinal microvascular abnormalities
 Microaneurysms & haemorrhages
 Neovascularization
 BLINDNESS

65. RENAL COMPLICATIONS
Individual with diabetic nephropathy almost always have diabetic retinopathy
Glomerular hyperfiltration
Increased glomerular capillary pressure
Proteinuria in individuals with DM is associated with markedly reduced survival &
increased risk for cardiovascular disease

67. Diabetes insipidus (DI)
Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of
severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes
inability of the kidney to concentrate urine. Diabetes insipidus (DI) is caused by a
deficiency of antidiuretic hormone (ADH), or by an insensitivity of the kidneys to that
hormone.

68. DIABETIC NEUROPATHY
 Both myelinated and unmyelinated nerve fibers are lost
 Distal sensory loss
.SYMPTOMS
Numbness,tingling,sharpness and burning that begins in the feet and spreads proximally
Worsens at night
 As diabetic neuropathy progresses the pain subsides & eventually disappears but a sensory dediciency in
the lower extremities persists
 Physical examination reveals sensory loss of reflex & abnormal position sense

69. CARDIOVASCULAR MORBIDITY & MORTALITY
peripheral arterial disease
Congestive heart failure
MI
Coronary arterial disease
Sudden death
American heart association recently declared DM as a risk
factor (type II)
The absence of chest pain (silent ishcemia) is common in
individuals with diabetes

72. GASTROINTESTINAL
delayed gastric emptying(gastro paresis)
altered small & large bowel motility(constipation or diarrhoea)
nocturnal diarrhoea alternating with constipation isa common feature
GENITOURINARY
diabetic autoneuropathy symptoms=inability to sense th e full bladder and
failure to void completely
as bladder contractility worsens bladder capacity and post void residual
increases leading to symptoms of urinary hesitancy
decreased voiding frequency
incontinence
recurrent urinary tract infection

73. LOWER EXTREMITY COMPLICATIONS
Neuropathy
Abnormal foot biomechanics
Peripheral arterial disease
Poor wound healing
Risk factor for foot ulcer
Male sex
Diabetic > 10 yrs
Peripheral vascular disease
Poor glycemic control

74. INFECTION
Pneumonia,UTI, skin & soft tissue infection are all common
Reasons
Incompletely defined abnormalities ,phagocyte function
Diminished vascularization
Hyperglycemia aids colonization & growth of various organisms
They have greater risk of post operative wound infection

75. Severe hypertriglyceridemia and chylomicronemia
(type V hyperlipidemia) – eruptive xanthomata
A 36 year old moderate drinker with diabetic ketoacidosis and acute pancreatitis.
Eruptive xanthomata in severe hypertriglyceridemia and chylomicronemia
(type V hyperlipidemia) due to uncontrolled diabetes mellitus (diabetic lipemia)

76. Thank you all……
Thank you all……
To be continued..