Diabetes is a condition characterized by hyperglycemia resulting from issues with insulin production or action. It can lead to pathological changes in tissues and complications like retinopathy, neuropathy, and cardiovascular disease. Insulin is a hormone produced in the pancreas that regulates glucose metabolism. It works by increasing glucose uptake and storage and inhibiting gluconeogenesis and lipolysis. Different insulin preparations have been developed with varying durations of action. Treatment of diabetes involves restoring normal metabolism through insulin administration and preventing complications.
COMPLICATIONS, MANAGEMENT AND TREATMENT APPROACH OF DIABETES MELLITUSAnas Indabawa
Diabetes describes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Mellitus is Latin for “sweet as honey”.
Pancreas is an elongated, tapered gland that is located behind the stomach and secretes digestive enzymes and the hormones insulin and glucagon.
The Pancreas secretes insulin and Glucagon directly into the blood stream.
It also secretes digestive enzymes into the pancreatic duct, which joins the common bile duct from the liver and drains into the small intestine.
Insulin and Glucagon have opposite effects on liver and other tissues for controlling blood-glucose levels.
COMPLICATIONS, MANAGEMENT AND TREATMENT APPROACH OF DIABETES MELLITUSAnas Indabawa
Diabetes describes a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body's cells do not respond properly to insulin, or both. Mellitus is Latin for “sweet as honey”.
Pancreas is an elongated, tapered gland that is located behind the stomach and secretes digestive enzymes and the hormones insulin and glucagon.
The Pancreas secretes insulin and Glucagon directly into the blood stream.
It also secretes digestive enzymes into the pancreatic duct, which joins the common bile duct from the liver and drains into the small intestine.
Insulin and Glucagon have opposite effects on liver and other tissues for controlling blood-glucose levels.
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Update on DIABETES MELLITUS (2020) By Dr Rahul Jain , Dr Sharda JainLifecare Centre
DEFINITION
CLASSIFICATION AND ETIOLOGY
PATIENT PROFILE
METABOLIC SYNDROME
CLINICAL FEATURES
DIAGNOSIS AND INVESTIGATIONS
DAWN AND SOMOGYI PHENOMENON
MANAGEMENT
COMPLICATIONS AND METABOLIC MEMORY
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Update on DIABETES MELLITUS (2020) By Dr Rahul Jain , Dr Sharda JainLifecare Centre
DEFINITION
CLASSIFICATION AND ETIOLOGY
PATIENT PROFILE
METABOLIC SYNDROME
CLINICAL FEATURES
DIAGNOSIS AND INVESTIGATIONS
DAWN AND SOMOGYI PHENOMENON
MANAGEMENT
COMPLICATIONS AND METABOLIC MEMORY
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June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
How to Make a Field invisible in Odoo 17Celine George
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The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
2. Diabetes mellitus
• Hyperglycaemia, glycosuria, hyperlipidaemia,
negative nitrogen balance and ketonaemia
• Pathological changes: thickening of capillary
basement membrane, increase in blood vessel
wall matrix, and cellular proliferation
• Consequences: Lumen narrowing,
atherosclerosis, sclerosis of glomerular
capillaries, retinopathy, neuropathy and
peripheral vascula insuffficency
3. Contd.
• Causes of pathological changes: Enhanced
non-enzymatic glycosylation of tissue proteins
and accumulation of large amounts of sorbitol
• Glycosylated haemoglobin (HbA1c ) – Index of
protein glycosylation
4.
5.
6.
7.
8.
9.
10. • Discovered by Banting and Best – 1921
• 2 chain Polypeptide – 51 amino acids & MW 6000
• Chain-A has 21 and Chain-B has 30 amino acids –
connected by two disulfide bonds
• Source: Porcine, Bovine and Human
• Synthesized in β cells of islets of pancreas – single
chain 110 amino acids (Preproinsulin)
• Proinsulin – 86 amino acids
• connecting or ‘C’ peptide (35 AA) is split off by
proteolysis in Golgi apparatus
• Both insulin and C peptide are stored in granules
within the cell
11.
12. Regulation of Secretion
• Basal condition – 1 U per hour – more after
meals
• Regulated by – Chemical, hormonal and
neural mechanisms
18. • Meal derived glucose, amino acids, fatty acids
and fuel storage
• Major anabolic hormone – synthesis of
glycogen, lipids and proteins
• Facilitates glucose transport across cell
membrane
– skeletal muscle and fats are highly sensitive
-Liver, brain, RBC, WBC and renal medullary cells are
independent
19. • Intracellular utilization of glucose is its
phosphorylation to form glucose- 6-
phosphate:
– enhanced by ↑ production of glucokinase
• facilitates glycogen synthesis from glucose in
liver, muscle and fat by stimulating the
enzyme glycogen synthase
• Inhibits glycogen degrading enzyme
phosphorylase → decreased glycogenolysis in
liver
• Inhibits gluconeogenesis from protein,
FFA and glycerol) in liver
20. • inhibits lipolysis in adipose tissue and favors
triglyceride synthesis
• Insulin deficiency
• increased FFA and glycerol in blood
• taken up by liver to produce acetyl-CoA
• Keton body formation &DKA
21. • Facilitates amino acid entry and their
synthesis to protein
• Inhibits protein breakdown in muscles and
other cells
22. Actions of insulin producing
hypoglycaemia
Liver Muscle Adipose tissue
•Increases glucose
uptake and glycogen
synthesis
•Inhibits glycogenolysi
•Inhibits
gluconeogenesis
from protein, pyruvate,
FFA
and glycerol
•Increases glucose
uptake and utilization
•Inhibits proteolysis and
release of amino acids
pyruvate, lactate into
blood
•Increases glucose
uptake and storage as
fat and glycogen
•Inhibits lipolysis and
release of FFA + glycerol
24. Fate of Insulin
• Distributed only extracellularly – given orally
gets degraded in GIT
• Secreted and injected Insulin – metabolized in
liver, kidneys and muscles
• First pass metabolism - 50% of Insulin passing
through portal vein
• Degradation after receptor mediated
internalization
25.
26. Preparations of Insulin
• Classically – produced from beef and pork
pancreas
• Contains 1% (10, 000 ppm) other proteins –
proinsulin, polypeptides, pancreatic proteins
etc.) – potentially antigenic
• Replaced with highly purified pork/beef
insulin/recombinant human insulin/insulin
analogues
27. Contd.
• Single peak and Monocomponent insulin (MC)
– proinsulin <10 ppm – stable, less resistance
and lipodystrophy
28. Unitage/Assay:
• I U reduces fasting rabbit blood sugar by 45
mg/dl or potency to induce hypoglycaemic
convulsion in mice
• I mg of International Standard of Insulin = 28
units
• Radioimmunoassay or enzyme immunoassay
29. Regular (Soluble) Insulin
• Buffered neutral pH solution unmodified insulin
stabilized by small amount of zinc
• Forms hexamers around zinc ions – released slowly and
gradually by dilution on SC administration
• Peak onset 2- 3 hours and lasts for 6-8 hours
• Drawbacks:
– Before meals – early postprandial hyperglycaemia and late
post prandial hypoglycaemia – injected ½ to 1 hour before
– Do not provide basal level of action – interdigestive period
– Do not provide basal level of action – interdigestive period
• To overcome:longacting ‘modified’ or ‘retard’
preparations of insulin used
30. Human Insulin
• Same amino acid sequence as human insulin -
produced by recombinant DNA technology
• In Es cherichia coli – proinsulin recombinant
bacteria (prb) and in yeast – precursor yeast
recombinant (pyr) or by enzymatic
modification of porcine insulin
• Human actrapid (regular insulin) – 40 U/ml
• HUMAN MIXTARD: Human soluble insulin
(30%) and isophane insulin (70%),
31. Advantages
• More water soluble and hydrophobic
• more rapid absorption than porcine or bovine
• more defined peak
• shorter duration of action
32. Insulin analogues
• Using recombinant DNA analogues of insulin
have been produced with modified
pharmacokinetic
• Greater stability and consistency are the other
advantages
33. Insulin lispro
• Produced by reversing proline and lysine at
the carboxy terminus B 28 and B 29 positions
• injected immediately before or even after the
meal
• lower incidence of late post-prandial
hypoglycaemia
• slightly greater reduction in HbA1c compared
to regular insulin
34. Insulin aspart
• proline at B 28 of human insulin is replaced by
aspartic acid
• Other properties & advantages are same
35. Insulin glulisine
• Replacing aspartic acid at B 23 by lysine and
glutamic acid replacing lysine at B 29
• continuous SC insulin infusion (CSII)
36. Insulin glargine
• Long- acting
• precipitates at neutral pH on SC injection
• depot is created from which monomeric insulin
dissociates slowly to enter the circulation
• Onset:delay
• Duration:24 hrs
• smooth ‘peakless’ effect
• suitable for once daily injection
37. Contd.
• Advantages:
• Lower incidence of night-time hypoglycaemic
episodes
• Disadvantages
• does not control meal-time glycaemia
• Because of acidic pH, it cannot be mixed with
any other insulin preparation
38. REACTIONS TO INSULIN
HYPOGLYCAEMIA:
• More in diabetics
• Causes: Injection of large doses, missing a meal
after injection, vigorous exercise
• Symptoms
– Sweating, anxiety, palpitation, tremor: Sympathetic
stimulation
– dizziness, headache, behavioral changes, visual
disturbances, hunger, fatigue, weakness, muscular
incoordination:glucose deprivation
– Below < 40 mg/dl:seizure and coma
40. Other side effects
• Local reactions :swelling, erythema and
stinging
• Lypodystrophy
• Allergy:
– due to contaminating proteins
– very rare with human/highly purified insulins
• Edema
41. Diabetes mellitus
Purpose:
• Restore metabolism to normal
• avoid symptoms due to hyperglycaemia
• prevent complications
Indications:
• Type 1 DM
• Post pancreatectomy diabetes and gestational
diabetes
42. Contd.
• Type 2 DM:
• Not controlled by diet and exercise,
• failure of oral hypoglycaemics,
• under Weight
• Temporarily to tide over infections, trauma, surgery,
pregnancy
• complication of diabetes, e.g. ketoacidosis, nonketotic
hyperosmolar coma, gangrene of extremities
• Dose:
– type:1: 0.4–0.8 U/kg/day
– Type 2 patients:0.2–1.6 U/kg/day
43. Regimen
• single daily injection of any
long/intermediate/ short-acting insulin or
mixture
• Either multiple (2-4) injections daily of long
and short acting insulins or a single injection
daily of long-acting insulin supplemented by
oral hypoglycaemics
44. Contd.
• total daily dose of a 30:70
or 50:50 mixture of
regular and NPH insulin is
usually split into two(Slit
mixed regimen)
• injected s.c. before
breakfast and before
dinner
45. Contd.
• Basal bolus regimen’ that is now advised
needs 3–4 daily injections
• long-acting insulin (glargine) is injected once
daily either before breakfast or before bed-
time for basal coverage along with 2–3 meal-
time injections of a rapid acting preparation
46. Other uses
• Diabetic ketoacidosis
• Hyperosmolar (nonketotic hyperglycaemic)
• coma
47. Insulin resistance
• Type 2 DM
• Age
• large body fats
• Pregnancy
• OCPs
• Rare causes:acromegaly, Cushing’s syndrome,
pheochromocytoma
48. Acute insulin resistance
• Infection, trauma, surgery, emotional stress,
and other hyperglycaemic hormones
• DKA
50. Diabetic ketoacidosis
• Common in type 1 DM
• Infrequent in type 2 DM
• Causes
• Infection
• Trauma
• Stroke
• Pancreatitis
• stressful conditions
• Inadequate doses of insulin
51.
52. Treatment
• Insulin:
– bolus dose of 0.1–0.2 U/kg i.v. is followed by 0.1
U/kg/hr infusion
– Within 4–6 hours blood glucose reaches 300
mg/dl rate of infusion is reduced to 2–3
U/hr
• Intravenous fluids:Normal saline is infused i.v.,
initially at the rate of 1 L/hr
– blood sugar has reached 300 mg/dl, 5% glucose in
½N saline
53. • KCl:After 4 hours 10–20 mEq/hr KCl to the i.v.
fluid
• Sodium bicarbonate
• Phosphate
• Antibiotics
• Treatment of precipitating cause
56. SULFONYLUREAS
• MECHANISM OF ACTION :
1) Main action on β-cells to stimulates insulin
secretion and reduces blood glucose.
• Reduces permeability of K+ by competitively
blocking sulfonylures receptor (SUR1) present
on ATP-sensitive K+ channels
Depolarization
57. • Enhances Ca +2 influx - degranulation
• Increase the rate of the insulin secretion
2) Suppress glucagon levels – contribute to
hypoglycemic effect
SULFONYLUREAS CONTIN..
58. 3) Bind to Sulfonylurea receptor on the K+
Channels in extra pancreatic cells
• Increase the number of insulin receptors on
target cells particularly in liver
4) 2nd generation SU have an additional effect of
increase sensitivity of peripheral tissue to the
insulin .
SULFONYLUREAS CONTI…
59. PHARMACOKINETICS
• Well absorbed Orally
• Highly Protein bound – 90-98%
• Low volume of distribution (0.2-0.4 L/kg)
• Onset of action is approximately 1-3 hrs
• Duration of action of second generation is
around 24 hrs
• Metabolized by the liver, and the metabolites
are excreted in the urine.
• second-generation agents are approximately
100 times more potent than first generation.
60. ADVERSE EFFECT
• Hypoglycemia : most common in elderly patients with
impaired renal and hepatic function with long acting agents
• Increase Weight : due to fluid retention and edma
• Hypersensitivity: photosensitivity,rash,purpura
• Chlorpropamide causes
cholestatic jaundice
dilutional hyponatremia
disulfuram like reaction
61. MEGLITINIDE ANALOGUES
• Quick and short acting insulin secretion
enhancers
• REPAGLINIDE : Action is similar to SU by
blocking ATP-sensitive potassium channels in
beta cells .
• Should be administered before each major
meal to control postprandial hyperglycemia.
• Dose should be omitted if a meal is missed.
• PK: metabolised by liver and excreted through
kidney .
62. • AE: hypoglycemia,headache,dyspepsia,arthralgia,
weight gain
• NATEGLINIDE :
• D-phenylalanine derivative.
• Stimulates 1st phase of insulin secretion
• So rapid onset and shorter duration of
hypoglycemic action than repaglinide .
• AE : dizziness, nausea, flu like symptoms,
hypoglycemia(rare)
MEGLITINIDE ANALOGUES
63. BIGUANIDES
MECHANISM OF ACTION :
Action is mediated by AMP dependent
kinase(AMPK)
Features
• Suppresses hepatic gluconeogenesis and glucose
output from liver
• Enhances insulin-mediated glucose uptake and
disposal in skeletal muscle and fat
– glycogen storage in skeletal muscle
– reduced lipogenesis in adipose tissue and enhanced
fatty acid oxidation
64. Contd.
• Interferes with mitochondrial respiratory
chain and promotes peripheral glucose
utilization through anaerobic glycolysis
• Other action
• also retards intestinal absorption of glucose,
other hexoses, amino acids and Vit B12
65. Adverse effects
• Abdominal pain, anorexia, bloating, nausea,
metallic taste,mild diarrhoea and tiredness
• In long term use – decrease absorption of
vitamin B12
67. USES
• Drug of choice of all all type 2 DM patients
Advantages of metformin are
• Nonhypoglycaemic
• weight loss promoting
• potential to prevent macrovascular as well as
microvascular complications of diabetes
• no acceleration of β cell exhaustion/ failure in
type 2 DM
• HbA1c reduction by 0.8–1.2%
68. Non-diabetic use :
• It is used to treat hirsutism in the patient with
PCOD and enhances the fertility in these
women by decreasing androgen level and
enhancing insulin sensitivity
69. α- Glucosidase Inhibitor
• MOA: It inhibits α -glucosidase enzyme which
facilitates digestion of complex starches ,
oligosaccharides and disaccharides into
monosaccharides which is important for
absorption .
• So, it reduces postprandial digestion and
absorption of carbohydrates and lowers the
post meal hyperglycemia.
• Pk: mainly excreted through kidney .
70. Adverse Effect :
• Flatulence ,Diarrhea
• Abdominal pain due to fermentation of
undigested carbohydrates in lower GIT
• Cutaneous hypersensitivity
C/I: Bowel obstruction
Inflammatory Bowel disease
Stage 4 renal failure
α- Glucosidase Inhibitor
71. THIAZOLIDENEDIONS
MOA :
1) Acts as agonist to a nuclear receptor called
Peroxisome Proliferator Activated Receptor-
gamma(PPAR-γ).
• Which is expressed mainly in adipose tissue,
skeletal muscle and liver.
• Activation of PPAR- γ promotes transcription
of insulin responsive genes which control
glucose and lipid metabolism.
72. THIAZOLIDENEDIONS
2) Also increase the number of GLUT-4 glucose
transporter in cell membrane of skeletal
muscles and adipose tissue, which promotes
peripheral uptake and utilization of glucose.
3) Also decrease hepatic glucose output by
inhibiting gluconeogenesis.
THIAZOLIDENEDIONS
73. • Insulin sensitizing action of glitazone takes several
weeks to develop.
Adverse Effect :
• Weight gain due to fluid retention and edma
• Increased deposition of subcutaneous fat and
hemodilution - reduction in Hemoglobin
concentration.
• Increase the risk of heart failure and MI
( Rosiglitazone withdrawl from market oct-2010)
• Hepatotoxicity , reduce bone density
THIAZOLIDENEDIONS
74. DPP-4 INHIBITORS
• DPP-4 is a serine protease that is widely
distributed throughout the body .
• They provide nearly complete and long lasting
inhibition of DPP-4 , increase the proportion
of active GLP-1 from 10-20% to nearly 100%.
• Sitagliptin and alogliptin are competitive
inhibitors of DPP-4 whereas vildagliptin and
and saxagliptin bind the enzyme covalently.
75.
76. DPP-4 INHIBITORS cont…
Mechanism of Action : Selective inhibition of DPP-4
enzyme which inactivates GLP-1 .
• As a result GLP-1 levels are increased and its actions
prolongs which is responsible for
1) Increase insulin secretion
2) decrease glucagon release
3) delay gastric emptying
4) decreases the appetite by acting at the level of
hypothalamus.
77. Adverse Effect : Nasopharyngitis (because
substance-p is also a substrate of DPP-4 whose
levels get elevated)
• GIT distress
• Diarrhoea
• Pancreatitis
DPP-4 INHIBITORS cont…
78. INCRETIN-MIMETICS
• Incretin is a group of hormone that includes
Glucagon like peptide-1 (GLP-1)
Glucose dependent Insulinotropic
polypeptide(GIP) that are released after
meals from GIT and augment glucose
dependent Insulin secretion.
• Among them GLP-1 is the prominent
insulinotropic incretin.
• It is metabolised by DPP-4 enzyme .
79. Thus GLP-1 agonist
1) Increase insulin secretion
2) decrease glucagon release
3) delay gastric emptying
4) decrease the appetite by acting at the level of
hypothalamus.
INCRETIN-MIMETICS
80. LIRAGLUTIDE
• It is given as a once daily injection .
• Peak level 8-12 hrs
• Elimination t1/2 is 12-14 hrs.
• Little , renal or intestinal clearance and it is
primarily through the metabolic pathways of
large plasma proteins.
• So, can be given safely in the patient with
renal failure
INCRETIN-MIMETICS