Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
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Diabetes mellitus
1.
2. History & epidemiology
Anatomy of PancreasAnatomy of Pancreas
Biochemistry & Physiology Of InsulinBiochemistry & Physiology Of Insulin
PathogenesisPathogenesis
Clinical Features & Lab diagnosisClinical Features & Lab diagnosis
Treatment & Management
Complications
Case presentationCase presentation
Prevention, Control & Recent Advances
4. Manipal Teaching HospitalManipal Teaching Hospital
OPD RecordOPD Record
â Name of the Patient :Sharmila Gharti Magar
â Age/sex : 55 yrs/F
â Weight : 79 Kg
â Height : 152 cm
ïBMI : 34 kg/m2
(Obese)
5. Presents to Department of Medicine with symptoms of:
â Fatigue
â Increased hunger
â Frequent urination
â Weight loss
â Exercise intolerance with shortness of breath for many
months
â Tingling sensation in extremities
â Blurred vision
9. ï§ Case was diagnosed as:Case was diagnosed as: Type 2 Diabetes MellitusType 2 Diabetes Mellitus
ï§ Rx:
ï§ Tab Metformin 500mg PO, Twice a day
ï§ Adv- Regular physical exercise and life style
modification.
ï§ Follow up- after 1 week
11. What is diabetes mellitus?
â It is a chronic metabolic disease in which high level of
glucose (sugar) build up in the bloodstream either due to
â Insulin Deficiency
â Insulin Resistance
â The high blood sugar produces the classical symptoms:
â Polyuria
â Polydipsia
â Polyphagia
12. TYPES OF DIABETESTYPES OF DIABETES
MELLITUSMELLITUS
â Diabetes Mellitus Type 1: There is deficiency
of insulin .
â Diabetes Mellitus Type 2: There is enough
insulin but cells are resistant to insulin.
â Gestational Diabetes: Develops during
pregnancy.
13. Other types of Diabetes MellitusOther types of Diabetes Mellitus
â LADA (Latent-Autoimmune Diabetes in
Adults)
â MODY (maturity-Onset Diabetes of youths)
â Other secondary diabetes mellitus
15. â The term DIABETES :Greek word for siphon, âto go
throughâ or âexcess discharge of urineâ
â MELLITUS: Latin word for âsweet as honeyâ
HISTORY OF DIABETESHISTORY OF DIABETES
MELLITUSMELLITUS
16. âBanting and Best - Isolated insulin 1st
time from
dogâs pancreas - on July 30,1921.
âSanger et al- Discovered the structure of insulin for
the 1st
time in 1951 A.D.
17. 1922 â Banting, Mc Leod, Best, Collip
shared the Nobel prize
Banting
Mc Leod
Best
Collip
21. ïFastest growing chronic disease that affects millions
of people worldwide.
ïDiabetes is a huge and growing problem.
ï50-80% donât know they have it !!
23. GLOBAL SCENARIO
ïCurrently number of estimated cases- around 387 million.
(IDF 2014)
ïThe expected increase in number is +205 million by
2035.
ï77% people with diabetes live in low and middle income
country
ïIn every 7 seconds 1 person dies from diabetes.
ïPeople death per year- 4.9 million.
ï50% of deaths - under age of 60 years.
24. PREVALENCE
â Male >female
â The global diabetes prevalence rate is 8.3%.
â People with DM live 7-8 years less than their non
diabetic peers.
27. According to the IDF (data publishedAccording to the IDF (data published
in April 2014)in April 2014)
In NepalIn Nepal
âąDiabetes cases are 700 thousand.
âąDiabetes related death (20-70 years age) are 14778.
In IndiaIn India
âąDiabetes cases are 66,846,880.
âąDiabetes related death (20-70 years age) are 1,039,980
28. WORLD DIABETES DAYWORLD DIABETES DAY
ï14th
November
ïBirthday of the man who co-
discovered insulin: Frederick
Banting
ïBlue circle : Universal symbol for
diabetes
ïThe color blue reflects the sky that
unites all nations.
 Recent theme :
2014-2016:Healthy Living and Diabetes
30. PANCREASPANCREAS
INTRODUCTION:
ï± French word: Pan-all and kreas â
flesh
ï± Retroperitoneal, soft, lobulated,
elongated
ï± Extension: Concavity of
duodenum to hilum of spleen
ï± Consists:
Exocrine and Endocrine parts
32. PARTSPARTS
Head, Neck, Body and Tail
ï± Head:
â Enlarged towards right and
occupies the concavity of
duodenum
Parts-
ï Surfaces - anterior & posterior
ï Borders-Upper ,lower,
right/lateral
ï Process â Uncinate process
33. Head- RelationsHead- Relations
â Anterior Surface:
o Gastroduodenal artery, transverse
colon, and jejunum
â Posterior surface:
o IVC, bile duct, Rt. crus of
diaphragm
â Upper border: 1st
part of duodenum, sup. Pancreatico duodenal
artery
â Lower border: 3rd
part of duodenum, inf pancreatico duodenal
artery
â Right lateral: 2nd
part of duodenum, bile duct, anastomosis of
pancreatico duodenal arteries
34. NeckNeck
â Constricted part of pancreas between head
and body
L = 2cm
â Parts:
Surfaces- anterior and posterior
Borders- upper and lower
â Relations:
Anterior surface:
ïLesser sac
ïPylorus
Posterior surface:
ïTermination of superior mesenteric vein
ïBeginning of portal vein
36. Body of pancreasBody of pancreas
Prismoid in appearance,Triangular
on CS
Extends from neck to tail i.e. aorta
to lt. kidney
ï”Parts-
ï3 surfaces- antero- superior ,
antero-inferior and posterior
ïBorders - superior, anterior &
inferior
37. Body- RelationsBody- Relations
ï Anterio- Superior surface
ï Lesser sac and Stomach
ï Anterio-Inferior surface:
ï Duodenojejunal flexure
ï Coils of jejunum and Lt. colic flexure
âą Posterior surface:
ï Abdominal aorta
ï Lt. crus of diaphragm
ï Lt. psoas major
ï Lt. sympathetic trunk
ï Lt. suprarenal gland
ï Lt. kidney across its hilum
ï Lt. renal vessels
ï Pelvis of lt. ureter
ï Lt. suprarenal vein
38. Tail of pancreasTail of pancreas
ï” Narrow left end of pancreas
ï” Lies in lienorenal ligament ,
opposite to T12, together with
splenic vessels
ï” Comes in contact with spleen
44. INSULININSULIN
â A Polypeptide hormone
â M.Wt-5808
â Composed up of 51 AA
â 2 chains i.e chain A (21)
chain B (30)
â Connected to each other by
disulphide linkages
45. SYNTHESIS OF INSULINSYNTHESIS OF INSULIN
â Synthesized in beta cell of islets of langerhans
â Translation of insulin RNA
(By Ribosomes attached to ER)
Preproinsulin(m.wt-11500)
Cleaving in ER
Proinsulin (m.wt-9000)
46. â Proinsulin = Peptide A + Peptide B + Peptide C
â Most of the Proinsulin cleaved in Golgi
apparatus to form Insulin and C Peptide
(Insulin=Peptide A -s-s- Peptide B)
â 5-10% released as Proinsulin.
48. Secretion of InsulinSecretion of Insulin
ï” 1st
Phase
o Within 2-3 mins of acute elevation in blood
glucose concentration, increases almost 10 times
ï” 2nd
Phase
o Decreases for sometime
o Again increases about 15 times and maintained
till blood glucose is high
49. TRANSPORT AND DISTRIBUTIONTRANSPORT AND DISTRIBUTION
â Binds with plasma protein: Synalbumin
â Half life=5-10min
â Plasma concentration=20-30microU/ML
â Fixed to many tissues but RBC and many of brain
cells do not bind to it
â Large amounts are bound to liver and kidney
â Exerts effect without entering cell on which it acts.
56. Catabolic hormonesCatabolic hormones
â Glucagon:
âPrimary hyperglycemic hormone
âReleased when blood glucose <70 mg/dl
âEpinephrine:
âSecondary early response hyperglycemic hormone
âMediated through hypothalamus
âCortisol and GH:
âLong term hyperglycemic hormone
âActivation takes hours to days
âEffect mediated through hypothalamus
âDecrease glucose utilization in most of the cells
58. Pathogenesis of Type I DMPathogenesis of Type I DM
ï An autoimmune disease
ï T cell-mediated progressive destruction of pancreatic ÎČ-cells
ï Manifest clinically â after loss of 80/90 % of ÎČ-cell mass
ÎČCellMass
Time
Development of type 1 diabetes
59. ï 1/3rd
of the susceptibility
ï 20 different regions of human genome show some linkage
ï Polymorphism in HLA region - accounts for 40-50 % risk
ï Other genes,
âą CD25, PTPN22, IL-2RA and IL-10
Genetic Factors
60. ï Have not been conclusively linked
ï Possible candidates include;
ï Virus - Mumps, Coxsackie B4, retroviruses, rubella
(in utero), CMV & EBV
âMOLECULAR MIMICRY â
ï Diet - Dietary nitrosamine, coffee
Environmental ConsiderationsEnvironmental Considerations
61. ï Bovine Serum Albumin (BSA)Bovine Serum Albumin (BSA)
ïŒ cross neonatal gut
ïŒ raise Ab
ïŒ cross-react with heat-shock protein
expressed by ÎČ cells.
63. Mechanisms of ÎČ - Cell Destruction
ï” Failure of self--tolerance in T cells specific for islet
Ag
ï” Initial activation - Peri-pancreatic lymph nodes
ï” Activated T cells - traffic to pancreas
ï” TH1 cells - secrete cytokines - injure ÎČ cells
ï” CD8+ cells - kill ÎČ cells directly
64. ï Heterogeneous group of
disorders
ï interplay of genetic &
environmental factors
ï Absence of an
autoimmune basis
Genetic
susceptibility,
obesity, Sedentary
lifestyle
TYPE 2 DIABETES
IR ÎČ
Insulin
resistance
ÎČ-cell
dysfunction
Pathogenesis of Type II DMPathogenesis of Type II DM
65. EtiopathogenesisEtiopathogenesis
âą Obesity
âą Sedentary lifestyle
âą Functional defects - tyrosine
phosphorylation, serine
phosphorylation
âą ÎČ cell mass, islet degeneration
âą Secretory defect - loss of normal
oscillating pattern of insulin
secretion
INSULIN RESISTANCE ÎČ - CELL DYSFUNCTION
TYPE II DIABETES MELLITUS
72. DifferencesDifferences:
Features Type 1
(IDDM)
Type 2
(NIDDM)
Age at onset <40 yrs >50 yrs
onset acute gradual
Body weight Normal or low Obese
Ketonuria common uncommon
Rapid death without
T/t with insulin
Yes No
Family history No Yes
73. Lab DiagnosisLab Diagnosis
CATEGORIES:
1)Test performed in blood/serum
A. Estimation of glucose by
GOD/POD
method:FPS,RBS,PPBS test.
B. Estimation of glycosylated
HbA1c
C. C peptide test
74. Fasting plasma glucose (FPG) testFasting plasma glucose (FPG) test
ï” Preferred method for diagnosing children, men, and
non pregnant women.
ï” The test measures blood glucose levels after an
overnight fast (no food intake for at least eight
hours).
75. Random blood glucose testRandom blood glucose test
ï” Measures blood glucose levels at any time of
day.
ï” Used in people with classic diabetes
symptoms such as excessive thirst, frequent
urination and unexplained weight loss.
77. Oral Glucose Tolerance TestOral Glucose Tolerance Test
(OGTT)(OGTT)
ïProcedure
1. A fasting blood sample is drawn
2. Subject is given 75 g glucose is dissolved in 300ml
of water
3. Blood sample are collected at interval for at least
2hrs.
79. C peptide TestC peptide Test
ï” Distinguishes between type1and type 2 DM
ï” Pancreas of patients with type 1 is unable to
produce insulin so have a decreased level of C-
peptide
ï” Whereas C-peptide levels in type 2 patients are
normal or higher than normal.
ï” Interpretation
Normal range for a c-peptide test:
0.51-2.72 nanograms per millilitre (ng/mL)
80. 2) Test performed in urine2) Test performed in urine
A. BENEDICT TEST-Color reaction test
B. ROTHERAâS TEST: Purple ring â presence of ketone
bodies
C. Microalbumin /Albumin protein- Nephropathy
D.DIPSTICK TEST:
âąSensitive to as little as 0.1% glucose in urine
âąResult: Different colour response of indicator strip
reflect glucose concentration
83. TYPES OF INSULINTYPES OF INSULIN
ïBovine Insulin (more antigenic)
ïPorcine Insulin (less antigenic)
ïHuman insulin : Made by rDNA technology
(BASED ON SOURCES)
85. INSULIN DELIVERYINSULIN DELIVERY
SYSTEMSYSTEM
ï” Insulin Syringes
ï” Direct subcutaneous insulin injection remains the
most common form of delivery, using a needle
and syringe.
ï” Site of injection:
Abdomen>Arm>Buttock>Thigh
ï” Other delivery system-
Insulin Pump,Transdermal Patch,
Nasal spray ,Insulin pen
86. Complications of InsulinComplications of Insulin
TherapyTherapy
1) Hypoglycemia :Symptoms include sweating, slurring
of speech, palpitations, tachycardia,restlessness
2) Insulin allergy : rare condition
Utricaria results from Histamine release from mast cells.
3) Immune Insulin resistance : Low titer of circulating IgG
anti-insulin antibodies that neutralize action of insulin
4) Lipodystrophy at injection sites : There is atrophy of
subcutaneous fatty tissues at site of injection
89. BIGUANIDESBIGUANIDES
ï” Metformin
ï” Suppresses hepatic gluconeogenesis and glucose output
from liver
ï” Enhance insulin mediated glucose disposal in muscle and
fat via GLUT-4, enhance GLUT-1 transport from
intracellular site to plasma membrane
ï” Retards intestinal absorption of glucose
ï” Promotes peripheral glucose utilization
ï” FIRST LINE THERAPY FOR TYPE 2 DM
92. Dietary ManagementDietary Management
ï” Carbohydrate 45-65% total daily calories
ï” Protein-15-20% total daily calories
ï” Fatsâless than 30% total calories,
saturated fats only 10% of total calories
ï” Fiberâlowers cholesterol, so preferred
ï” Consistent, well-balanced small meals
several times per day.
ï” Salt intake less than 6 gm per day
A Plate Model for Meal
Planning
93. Exercise and DiabetesExercise and Diabetes
ï” Exercise increases uptake of glucose by
muscles and improves utilization and alters
lipid levels.
ï” Check BS before, during and after
exercising if the exercise is prolonged
95. Stress ManagementStress Management
ï” Behavioral modification
ï” Positive thinking
ï” Meditation
ï” Satisfactory treatment plans and special
attention
ï” Optimal family support and counseling
96. Glucose monitoringGlucose monitoring
ï” Patients on insulin should
check sugars 2-4 times per day.
ï” Not on insulin, two or three
times a week.
ï” Should check before meals and 2
hours after meals.
ï” HbA1 C measures blood glucose over
2-3 months.
97. Pharmacological management approaches in DMPharmacological management approaches in DM
ï” Fig: Flow chart of management approach in diabetes mellitus
ï” BG: Biguanide SU: Sulfonylureas TZD: Thiazolidinedione PP : Postprandial
98. Targets for Glycemic (blood sugar) ControlTargets for Glycemic (blood sugar) Control
In Most Non-Pregnant Adults:In Most Non-Pregnant Adults:
Factors ADA Guidlines
A1c (%)
<7*
Fasting (preprandial) plasma
glucose 70-130 mg/dL
Postprandial (after meal)
plasma glucose <180 mg/dL
*<6 for certain individuals
99. Teaching Plan to patientsTeaching Plan to patients
ï”Foot care, eye care, general hygiene, risk factor
management
ï”Recognition, treatment and prevention of acute
complications
ï”When to call the doctor
103. Diabetic ketoacidosis (DKA)Diabetic ketoacidosis (DKA)
ï MEDICAL EMERGENCY!!!
ï Characterized by:
âą Hyperglycemia
âą Ketosis
âą Metabolic acidosis
ï Most often seen in Type 1 DM
104. Non- ketotic hyperosmolarNon- ketotic hyperosmolar
diabetic coma (HHS)diabetic coma (HHS)
ïCharacterized by:
ïHyperglycemia
ïHyperosmolarity
ïDehydration without ketosis
ïSeen in Type 2 DM
108. HypoglycemiaHypoglycemia
ï” Most commonly in Type 1 DM patients treated
with insulin injections.
ï” Signs/Symptoms :
ï” Anxiety
ï” Tachycardia , Palpitation
ï” Sweating
ï” Weakness, lethargy
ï” Blurred vision
109. Treatment of Acute complicationsTreatment of Acute complications
ï Hypoglycemia:
âą If patient is conscious : 15 gm of sugar and wait for 15 minutes
âą If patient is not concious: 25 %â 50% glucose IV, followed by
infusion of 5% dextrose in water
ï Diabetic ketoacidosis:
âą Administration of short acting insulin
âą Fluid replacement
âą Potassium replacement
ï Non- ketotic hyperosmolar diabetic coma
âą Similar to ketoacidosis except:
âą Faster fluid replacement
âą NaHCO3 usually not required
âą Heparin (subcutaneous)
112. Macrovascular diseasesMacrovascular diseases
ï” Ischemic Heart Disease :
ï” 4 times increased risk of MI compared to
general population.
ï” Greater incidence of âSilent MIâ
ï”Likely due to sensory neuropathy
ï”May present as CHF
ï” Cerebro-vascular disease
ï” Peripheral vascular disease
114. Diabetic RetinopathyDiabetic Retinopathy
ï Diabetes is the leading cause of blindness in the working population of the
Western world.
ï Diabetic retinopathy is characterized by:
ï Abnormal retinal vascular permeability
ï Microaneurysm
ï Neovascularization
ï Hemorrhage & Scarring
ï Types:
ï Non proliferative:
ï Proliferative:
115. Diabetic NephropathyDiabetic Nephropathy
ï” Most common cause of end stage renal disease
ï” First indicator: microalbuminuria
ï” Glomerular changes that occur are:
ï” Capillary basement membrane thickening
ï” Diffuse Glomerularsclerosis
ï” Nodular Glomerulosclerosis
ï” Also known as Kimmelstiel-Wilson syndrome
116. Diabetic NeuropathyDiabetic Neuropathy
ïTypes:
ïPeripheral neuropathy:
ïMay manifest as Polyneuropathy or Mononeuropathy
ïAutonomic neuropathy:
ïMay cause hypoglycemia unawareness subjecting the
patient to the risk of severe hypoglycemia.
117. Lower extremity complicationsLower extremity complications
âą Diabetic foot ulcers are leading cause of
non traumatic lower extremity amputation
in US.
âąDiabetic foot ulcers are due to:
âąLoss of protective sensation due to
Peripheral neuropathy
âąPoor blood flow or ischemia due to
Peripheral vascular disease
118. Glycemic Control and Complications:Glycemic Control and Complications:
ïLong term complications depend upon the
duration of diabetes and state of glycemic
control.
ïDiabetic retinopathy , nephropathy and
neuropathy are irreversible.
ïGlycemic control can only reduce the rate of
progression of retinopathy and nephropathy.
121. Why Should we prevent
Diabetes?
ï” To reduce human suffering.
ï” To alleviate the economic burden.
ï” To prevent morbidity and mortality from
diabetes-related chronic vascular diseases
123. Primary PreventionPrimary Prevention
âąHealth Promotion & Specific Protection
âąTwo strategies suggested:
ïĄ Population Strategy
ïĄ High Risk Strategy
âą High risk Group :
ïĄ Age group of 40 and above
ïĄ Family history of DM
ïĄ Obese
ïĄ Women with excess weight gain during pregnancy
ïĄ Patient with premature atherosclerosis
124. Population StrategyPopulation Strategy
ï” Scope for Primary prevention in Type1 limited.
ï” More important in Type 2 DM.
ï” Measures include:
ï” Life style Interventions
ï” Weight reduction
ï” Physical Exercise
ï” Nutrition
ï” Education
126. Physical ExercisePhysical Exercise
âą Helps to increase insulin sensitivity and aids in
weight loss.
âą Insulin sensitivity persists hours after exercise
127. High Risk StrategyHigh Risk Strategy
ï No special high risk strategy for type 1 DM
ï More concerned with type 2 DM since it is related to:
âą Sedentary life style
âą Over nutrition and obesity
ï Avoid use of alcohol
ï Diabetogenic drugs like OCPs should be avoided.
ï Control atherosclerosis inducing factors:
ïSmoking
ïHigh BP
ïElevated cholesterol and TGs levels
128. Secondary PreventionSecondary Prevention
ï Early diagnosis and treatment
ï Aims of treatment:
ï Maintain blood glucose levels
ï Maintain ideal body weight
ï Treatment based on:
ï Diet alone
ï Diet and oral antidiabetic drugs
ï Diet and insulin
129. ï” Proper management
ï” Routine check up: Every 3 months
ï”Blood sugar
ï”Serum Creatinine
ï”Urine for proteins and ketones : Yearly
ï”Blood pressure : Every 3 months
ï”Visual acuity : Yearly
ï”Foot examination
ï”Skin examination : Every 3 months
ï” Glycosylated Haemoglobin estimation :
ï”Every 6 months
136. FUTURE PROSPECTFUTURE PROSPECT
ï” Tolrestat has been recently approved for the prevention of
diabetes complication.
e.g: Diabetes retinopathy, neuropathy, nephropathy.
137. ïBeta cell transplantation and incorporation of insulin
gene :
ï Which have tremendous potential in treatment of DM
ï Provide long lasting endogenous source of insulin in
both Type-1 and Type -2 patient.
138. CONCLUSIONCONCLUSION
ï” What an irony!!
âCells are swimming in glucose but are starving
to death because of impairment in uptakeâ