a presentation about type 2 DM.

1. DR.MUKESH KUMAR SAMOTA
MD(INTERNAL MEDICINE)
MEDICAL COLLEGE , JHALAWAR
RAJASTHAN(INDIA)

2. SCHEME OF PRESENTATRION :
1.INTRODUCTION AND DEFINITION OF DM
2.EPIDEMIOLOGY
3.GENETIC CONSIDERATION
4.PATHOPHYSIOLOGY
5. RISK FACTORS
6.APPROACH TO PATIENT
7.MANAGMENT
8NON PHARMACOLOGICAL
9 PHARMACOLOGICAL
10PREVENTION AND SCREENING
11.COMPLICATIONS
12.MANAGMENT OF COMPLICATIONS

3. INTRODUCTION:
Diabetes mellitus (DM) refers to a group of common
metabolic disorders that share the phenotype of
hyperglycemia.
Caused by a complex interaction of genetics and
environmental factors.
Depending on the etiology of the DM, factors
contributing to hyperglycemia include reduced insulin
secretion, decreased glucose utilization, and increased
glucose production

4. TYPE 2 DM
Type 2 DM is a heterogeneous group of disorders
characterized by variable degrees of insulin resistance,
impaired insulin secretion, and increased glucose
production.
Distinct genetic and metabolic defects in insulin action
and/or secretion give rise to the common phenotype of
hyperglycemia in type 2 DM

5. EPIDEMIOLOGY
The worldwide prevalence of DM has risen dramatically over the
past two decades
Prevalence of type 2 DM is rising much more rapidly, presumably
because of increasing obesity, reduced activity levels as countries
become more industrialized, and the aging of the population
In 2013, the prevalence of diabetes in individuals from age 20–79
ranged from 23 to 37%
The countries with the greatest number of individuals with
diabetes in 2013 are China (98.4 million), India (65.1 million),
United States (24.4 million), Brazil (11.9 million)

6. The prevalence is similar in men and women
throughout most age ranges
Diabetes is a major cause of mortality
Diabetes was listed as the seventh leading cause
of death in 2010
A recent estimate suggested that diabetes was
responsible for almost 5.1 million deaths or 8% of
deaths worldwide in 2013

7. GENETIC CONSIDERATIONS :
Type 2 DM has a strong genetic component.
The concordance of type 2 DM in identical twins is between 70
and 90%.
Individuals with a parent with type 2 DM have an increased risk
of diabetes; if both parents have type 2 DM, the risk
approaches 40%
The disease is polygenic and multifactorial, because in addition
to genetic susceptibility, environmental factors (such as obesity,
nutrition, and physical activity) modulate the phenotype

8. RISK FACTORS

9. PATHOPHYSIOLOGY
Type 2 DM is characterized by impaired insulin secretion due to B
cell dysfunction, insulin resistance at peripheral receptors that
leads to excessive hepatic glucose production, and abnormal fat
metabolism.
In the early stages of the disorder, glucose tolerance remains near-
normal, despite insulin resistance, because the pancreatic beta
cells compensate by increasing insulin output
As insulin resistance and compensatory hyperinsulinemia
progress, the pancreatic islets in certain individuals are unable to
sustain the hyperinsulinemic state.

10. Then develops IGT, characterized by elevations in
postprandial glucose,
A further decline in insulin secretion and an increase in
hepatic glucose production lead to overt diabetes with
fasting hyperglycemia.
Ultimately, beta cell failure ensues.
Although both insulin resistance and impaired insulin
secretion contribute to the pathogenesis of type 2 DM,
the relative contribution of each varies from individual
to individual.

11. 1. METABOLIC ABNORMALITIES
A. ABNORMAL MUSCLE AND FAT METABOLISM
Insulin resistance --->> impairs glucose utilization by insulin-sensitive tissues
and increases hepatic glucose output; both effects contribute to the
hyperglycemia.
Insulin receptor levels and tyrosine kinase activity in skeletal muscle are
reduced
“Postreceptor” defects in insulin-regulated
phosphorylation/dephosphorylation
Accumulation of lipid within skeletal myocytes, which may impair
mitochondrial oxidative phosphorylation and reduce insulin-stimulated
mitochondrial ATP production.
Obesity The increased adipocyte mass leads to increased levels of
circulating free fatty acids and other fat cell products (nonesterified free
fatty acids, retinolbinding protein 4, leptin, TNF-α, resistin, IL-6, and
adiponectin

12. B.IMPAIRED INSULIN SECRETION
A second genetic defect— superimposed upon insulin
resistance—leads to beta cell failure.
Beta cell mass is decreased by approximately 50% in
individuals with longstanding type 2 DM.
Islet amyloid polypeptide or amylin, co-secreted by the
beta cell, forms the amyloid fibrillar deposit found in
the islets of individuals with long-standing type 2 DM.
“Glucose toxicity” and “lipotoxicity”) and dietary fat
may also worsen islet function

13. C.INCREASED HEPATIC GLUCOSE AND LIPID PRODUCTION
Insulin resistance in the liver reflects the failure of
hyperinsulinemia to suppress gluconeogenesis, which results in
fasting hyperglycemia and decreased glycogen storage by the
liver in the postprandial state.
Adipose tissue->> lipolysis and free fatty acid flux from
adipocytes are increased, leading to increased lipid (very-low-
density lipoprotein [VLDL] and triglyceride) synthesis in
hepatocytes
leads to dyslipidemia] (elevated triglycerides, reduced high-
density lipoprotein [HDL], and increased small dense low-
density lipoprotein [LDL] particles

14. APPROACH TO THE PATIENT
HISTORY:-
 Attention should be directed to symptoms related to
diabetes (acute and chronic) and classifying the type
of diabetes by proper history and GPE.
 DM and its complications produce a wide range of
symptoms and signs; those secondary to acute
hyperglycemia may occur at any stage of the disease,
whereas those related to chronic hyperglycemia begin
to appear during the second decade of hyperglycemia

15. SIGN AND SYMPTOMS
 Polydipsia.
 Polyuria.
 Weight gain/lose
 Fatigue.
 Weakness.
 Blurry vision.
 Frequent superficial infections (vaginitis, fungal skin
infections).
 Slow healing of skin lesions after minor trauma.
 Metabolic derangements relate mostly to hyperglycemia
(osmotic diuresis) and to the catabolic state of the patient
(urinary loss of glucose and calories, muscle breakdown
due to protein degradation and decreased protein
synthesis).

16. PAST HISTRORY: -
In a patient with established DM, the initial assessment should also
include special emphasis on
 Prior diabetes care.
 Type of therapy-OHA/insulin
 Prior HbA1c levels.
 Self-monitoring blood glucose results.
 Frequency of hypoglycemia.
 Presence of DM-specific complications.
 Assessment of the patient’s knowledge about diabetes, exercise, and
nutrition.
 Presence of DM-related comorbidities and complications should be
sought
1) Cardiovascular disease,
2) Hypertension,
3) Dyslipidaemia,
4) CKD,
5) Ophthalmopathy ,
6) CVA).

17. FAMILY HISTORY:
 History of DM in 1st degree and sibling of patients
should obtained in detailed as
 History of HTN,DYSLPIDEAMIA,OBESITY,CAD , PTB
PERSONAL HISTORY:
 Diet/nourishment/change in weight
 Smoking/tobacco
 Alcohal use
 Menstrual /obstetrics history in female

18. OCCUPATIONAL HISTORY:
PHYSICAL EXAMINATION
 Complete physical examination
 Built and nourishment
 Weight/height/BMI/WC/HC/WHR
 Facial examination- symmetry/pallor /cyanosis/icterus/ teeth/gum/
 Peripheral pulses and blood pressure in all for limbs
 LAP
 Examination neck for swelling/LAP/scar marks/dilated veins/JVP/ neck circumference
 Chest and abdomen for shape/symmetry/scar marks/dilated vein/hernia/visible
pulsation/insulin injection site/organomegaly
 Examination of hand for clubbing/cyanosis/nail changes.
 Groin and genital
 Legs for assessment of blood flow/oedema/scar marks/ulcer/dilated veins/ look for the
presence of foot deformities such as hammer or claw toes / Charcot foot; and identify
sites of potential ulceration/nail care

19. SYSTEMIC EXAMINATIONS:
 Skin and mucus membrane for skin changes/uleration
 Eye: fundus/retinal/corneal/examination
 Cvs examinations
 Respiratory system
 CNS:
 sensation (vibratory sensation [128-MHz tuning fork at the
base of the great toe].
 The ability to sense touch with a monofilament [5.07, 10-g
monofilament].
 Pinprick sensation.
 Testing for ankle reflexes.
 Vibration perception threshold using a biothesiometer),
 Ankle reflexes.

20.  LABORATORY ASSESSMENT:

21. B. OTHER RELEVANT INVESTIGATIONS:
 HbA1c
 Cbc
 Lipid profile
 Urine albumin and sugar
 Thyroid function test
 Serum insulin ,glucagon
 C-peptide level
 Ecg,2 D echocardiography.
 Serum electrolytes.
 LFT/RFT
 Chest xray.
 C-reactive protein
 Islet cell autoantibodies ICAs(GAD, insulin, IA-2/ICA-512, and ZnT-8
serve as a marker of the autoimmune process of type 1 DM)
 UPT in case of female.

22. MANAGEMENT AND THERAPIES
OVERALL GOALS
 The goals of therapy for type 1 or type 2 diabetes
mellitus (DM) are to
 (1) eliminate symptoms related to hyperglycaemia.
 (2) reduce or eliminate the long-term micro vascular
and macro vascular complications of DM .
 (3) allow the patient to achieve as normal a lifestyle as
possible.

23. COMPREHENSIVE MEDICAL CARE FOR PATIENTS WITH DIABETES
 Optimal and individualized glycaemic control
 Self-monitoring of blood glucose (individualized frequency)
 HbA1c testing (2–4 times/year)
 Patient education in diabetes management (annual);
diabetes-self management education and support
 Medical nutrition therapy and education (annual)
 Eye examination (annual or biannual)
 Foot examination (1–2 times/year by physician; daily by
patient)
 Screening for diabetic nephropathy (annual)
 Blood pressure measurement (quarterly)
 Lipid profile and serum creatinine (estimate GFR)
(annual)
 The ADA recommends annual screening for distal symmetric
neuropathy beginning with the initial diagnosis of diabetes and annual
screening for autonomic neuropathy at the time of diagnosis of type 2
DM.
 Influenza/pneumococcal/hepatitis B immunizations
 Consider antiplatelet therapy

24. PREVENTION
Type 2 DM is preceded by a period of IGT or IFG, and a
number of lifestyle modifications and pharmacologic agents
prevent or delay the onset of DM
patients who had increased risk of diabetes should be reduce
body weight and increase physical activity as well as being
screened for cardiovascular disease
The ADA has suggested that metformin be considered in
individuals with both IFG and IGT who are at very high risk
for progression to diabetes (age <60 years, BMI ≥35 kg/m2,
family history of diabetes in first-degree relative, and women
with a history of GDM).
Individuals with IFG, IGT, or an HbA1c of 5.7–6.4% should be
monitored annually to determine if diagnostic criteria for
diabetes are present.

25.  TREATMENT GOALS FOR ADULTS WITH
DIABETES

26. PATIENT EDUCATION ABOUT DM, NUTRITION, AND
EXERCISE:
 The patient with type 1 or type 2 DM should receive
education about
 Nutrition.
 Exercise.
 care of diabetes during illness.
 medications to lower the plasma glucose.

27. NUTRITIONAL RECOMMENDATIONS FOR ADULTS WITH DIABETES OR
PREDIABETESA
A. Weight loss diet (in prediabetes and type 2 DM) /minimize weight gain (or T1DM)
 Hypo caloric diet that is low-carbohydrate and modest weight lose(5-7%)
B. Fat in diet (optimal % of diet is not known; should be individualized)
 Minimal trans fat consumption
 Mediterranean-style diet rich in monounsaturated fatty acids may be
better
C. Carbohydrate in diet (optimal % of diet is not known; should be individualized)
 Monitor carbohydrate intake in regard to calories
 Sucrose-containing foods may be consumed with adjustments in insulin
dose, but minimize intake
 Amount of carbohydrate determined by estimating grams of carbohydrate
in diet (type 1 DM)
 Use glycaemic index to predict how consumption of a particular food
may affect blood glucose
 Fructose preferred over sucrose or starch
D. Protein in diet (optimal % of diet is not known; should be individualized)
E. Other components
 •Dietary fiber, vegetable, fruits, whole grains, dairy products, and
sodium intake as advised for general population
 •Nonnutrient sweeteners
 •Routine supplements of vitamins, antioxidants, or trace elements not
advised

28. EXERCISE:
Exercise has multiple positive benefits including
i. cardiovascular risk reduction,
ii. reduced blood pressure,
iii. maintenance of muscle mass,
iv. reduction in body fat, and weight loss.
 For individuals with type 1 or type 2 DM, exercise is also useful
for lowering plasma glucose (during and following exercise) and
increasing insulin sensitivity.
 In patients with diabetes, the ADA recommends 150 min/week
(distributed over at least 3 days) of moderate aerobic physical
activity with no gaps longer than 2 days..
 Untreated proliferative retinopathy is a relative contraindication
to vigorous exercise, because this may lead to vitreous
haemorrhage or retinal detachment.

29.  PHARMACOLOGIC TREATMENT OF TYPE 2
DIABETES

30. A. ORAL HYPOGLYCAEMIC DRUGS
 Insulin secretagogues
 Insulin sensitizers
 Decrease glucose production
B. INJECTABLE AGENTS
 Insulin
 GLP-1 Agonist/incretins – Exenatide
 Amylin Agonist - Pramlintide

32. MOA OF INSULIN SECRETAGOGUES :

33. INSULIN SECRETAGOGUES:
 agents that affect the atp-sensitive k+ channel
SULFONYLUREAS:
First-generation :chlorpropamide, tolazamide, tolbutamide
Second-generation:
Glibenclamide (Glyburide) 2.5 -15mg (1-2)
Glipizide 5-20 mg (1-2)
Gliclazide 40-240mg [1-2]
Glimepirid1-6mg[1-2]
More rapid onset of action
Better coverage of the postprandial glucose rise,
Shorter half-life of some agents may require more than once-
a-day dosing.
Reduce both fasting and postprandial glucose and should be
initiated at low doses

34.  Sulfonylureas increase insulin acutely and thus
should be taken shortly before a meal; with
chronic therapy, though, the insulin release is
more sustained
 S/E hypoglycemia
Weight gain
 Contraindications :Renal/liver disease

35. NONSULFONYLUREAS[MEGLITINIDE]
 ↑ Insulin secretion
 Nateglinide 180-480 mg[3-4]
 Repaglinide 1-8mg[3-4]
 mitiglinide
 Short onset of action
 lower postprandial glucose
S/E Hypoglycemia
C/I Renal/liver disease

36. GLUCAGON LIKE PEPTIDE-1 (GLP-1) : INCRETIN
 secreted by L cells located in the distal GI tract (ileum and colon) in
response to ingested glucose.
 Releases insulin by binding to its specific receptor (GLP-1R)
 Slow gastric emptying
 Supress appetite
 Decrese glucagon
 Weight loss
MOA: It is positively coupled to increase in intracellular cAMP and
Ca2+levels in β cells.
Exenatide: analouge of glp1
Liraglutide : synthetic
Daluglutide
Parentral use [sc]
S/E: increase risk of hypoglycemia
C/I: renal disease
Agents that also slow GI motility;
Medullary carcinoma of thyroid

37. DIPEPTIDYL PEPTIDASE IV INHIBITORS[DPP 𝟒]
 Inhibit degradation of native incretins
 Prolong endogenous GLP-1 action and insulin secration
 Prefrential effect on PP glucose
 Weight gain.
Eg Sitagliptin 100 mg daily PO
Vildagliptin 50 mg[1-2]
 Alogliptin, Anagliptin, Gemigliptin, linagliptin,
saxagliptin, sitagliptin, teneligliptin, vildagliptin
 Well tolerated, do not cause hypoglycemia
 C/I: Reduced dose with renal disease;
 Associated with increase heart failure risk;
 Possible association with ACE inhibitor– induced
angioedema

38. INSULIN SENSITIZERS
BIGUANIDES : Metformin
 Mechanism of Action : Metformin activates AMP-
dependent protein kinase
 It reduces hepatic glucose production
 Improves peripheral glucose utilization
 It reduces fasting plasma glucose (FPG) and insulin levels.
 Improves the lipid profile, and promotes modest weight
loss.
 side effects :diarrhea, anorexia, nausea, metallic taste
 The major toxicity :lactic acidosis,. Vitamin B12 levels
decrease
 Contraindications: renal insufficiency (glomerular filtration
rate [GFR] <60 mL/min), any form of acidosis, unstable
congestive heart failure (CHF), liver disease, or severe
hypoxemia.

39. THIAZOLIDINEDIONES:
MOA: ↓ Insulin resistance to the PPAR Y[peroxisome
proliferative activated receptor –y],
↑ glucose utilization
 Rosiglitazone: asso with s/e MI CHF, STROKE
 pioglitazone; may have risk of blader cancer
 Improve glucose entry to fat tissue
 Hepatic gluconeogenesis decrease
 FA and lipolysis decrease
 Decrease TG
 Lower insulin requirements
S/E: hepatotoxity,Peripheral edema, CHF, weight gain,
fractures, macular edema
C/I :CHF, liver disease

40. DECREASE GLUCOSE PRODUCTIONS
Α-GLUCOSIDASE INHIBITORS:
 MOA: ↓ GI glucose absorption PP by inhibiting enzyme
oligosaccharidese that cleavage oligosaccharides into simple
suger
 Reduce postprandial glycemia
 Acarbose 50-100 mg. TDS PO
 Miglitol 25-100 mg TDS PO
 voglibose 200-300 microgm TDS PO
 These itself never cause hypoglycemia but can cause with insulin
secretagogues
 S/E diarrheal
 Flatulence
 Abd distension
 C/I:
 IBD/Renal/liver disease

41. MISCELLANEOUS ANTIDIABETIC DRUGS
AMYLIN ANALOGUE: It is produced by pancreatic B
cell and acts in the brain to
• Reduse glucagon secration from A cells
• Delayed gastric emptying
• Retard glucose absorption
• Promote satiety
PRAMLINITIDE
 reduce postprandial glycemic excursions in type 1 and
type 2 diabetic patients taking insulin.
 In type 2 DM, pramlintide is started as a 60-μg SC
injection before each meal and may be titrated up to a
maximum of 120 μg
The major side effects are nausea and vomiting

42. SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS
(SLGT2)
MOA:
lower the blood glucose by selectively inhibiting this co-
transporter, which is expressed almost exclusively in the
proximal, convoluted tubule in the kidney.
This inhibits glucose reabsorption, lowers the renal threshold
for glucose, and leads to increased urinary glucose excretion.
Due to the increased urinary glucose, urinary or vaginal
infections are more common, and the diuretic effect can lead
to reduced intravascular volume.
As part of the FDA approval of canagliflozin in 2013,
postmarketing studies for cardiovascular outcomes and for
monitoring bladder and urinary cancer risk are under way

43. Bile acid–binding resins:
 The bile acid–binding resin colesevelam has been
approved for the treatment of type 2 DM (already
approved for treatment of hypercholesterolemia).
 Because bile acid–binding resins are minimally
absorbed into the systemic circulation, how bile acid–
binding resins lower blood glucose is not known.
Bromocriptine:
• A formulation of the dopamine receptor agonist
bromocriptine (Cycloset) has been approved by the
FDA for the treatment of type 2 DM.
However, its role in the treatment of type 2 DM is
uncertain

44. INSULIN THERAPY IN TYPE 2 DM
Insulin should be considered as the initial therapy in
type 2 DM, particularly in
 lean individuals
those with severe weight loss
 In individuals with underlying renal or hepatic disease
that precludes oral glucose-lowering agents,
 In individuals who are hospitalized or acutely ill.
Insulin therapy is ultimately required by a substantial
number of individuals with type 2 DM because of the
progressive nature of the disorder and the relative
insulin deficiency that develops in patients with long-
standing diabet

45.  Insulin is usually initiated in a single dose of long-
acting insulin (0.3–0.4 U/kg per day), given in the
evening (NPH) or just before bedtime (NPH, glargine,
detemir).
The insulin dose may then be adjusted in 10%
increments as dictated by SMBG results.
Both morning and bedtime long-acting insulin may be
used in combination with oral glucose-lowering
agents.
Initially, basal insulin may be sufficient, but often
prandial insulin coverage with multiple insulin
injections is needed as diabetes progresses

47. INSULIN DEGLUDEC
An ultralong-acting basal Insulin analogue being developed
by Novo Nordisk under the brand name Tresiba.
One amino acid is deleted and conjugated to
hexadecanedioic acid via gamma-L-glutamyl spacer at the
amino acid lysine at position B29.
Lysine at the B29 position allows for the formation of multi-
hexamers in subcutaneous tissues
Results in slow insulin release into the systemic circulation.
Duration of action up to 40 hour. administered via
subcutaneous injection.

48.  CHOICE OF INITIAL GLUCOSE-LOWERING AGENT

49.  The level of hyperglycemia and the patient’s
individualized goal should influence the initial choice
of therapy.
 Assuming that maximal benefit of MNT and increased
physical activity has been realized, patients with mild
to moderate hyperglycemia (FPG 200–250 mg/dL)
often respond well to a single, oral glucose-lowering
agent. Patients with more severe hyperglycemia (FPG
250 mg/dL) stepwise approach that starts with a single
agent and adds a second agent to achieve the glycemic
target can be used.
 Insulin can be used as initial therapy in individuals
with severe hyperglycemia (FPG 250–300 mg/dL) or in
those who are symptomatic from the hyperglycemia.

50. COMBINATION THERAPY WITH GLUCOSE-LOWERING
AGENTS
 A number of combinations of therapeutic agents are
successful in type 2 DM
 Mechanisms of action of the first and second agents
should be different, the effect on glycemic control is
usually additive
 Titration of single agent to a maximum dose and then
addition of a second agent is used to achieve glycemic
control
 If adequate control is not achieved with the
combination of two agents (based on reassessment of
the HbA1c every 3 months), a third oral agent or basal
insulin should be added

51. EMERGING THERAPIES
 Bariatric surgery for obese individuals with type 2 DM
has shown considerable promise, sometimes with
dramatic resolution of the diabetes or major
reductions in the needed dose of glucose-lowering
therapies
 Several large, unblinded clinical trials have
demonstrated a much greater efficacy of bariatric
surgery compared to medical management in the
treatment of type 2 DM; the durability of the diabetes
reversal or improvement is uncertain
 The ADA clinical guidelines state that bariatric surgery
should be considered in individuals with DM and a
body mass index >35 kg/m2

52. THANK YOU