Diabetes Flashcards
Give a brief history of diabetes
Clinical features similar to diabetes mellitus described more than 3500yrs ago by ancient Egyptians .
•Indians/Arabs – had also described it , eg Avicenna , an arabian physician described among other things the complications – peripheral neuropathy, gangrene and erectile dysfunction
•Araetus of Cappodocia( 81-133AD)- named it Diabetes- TO SIPHON(named so cuz the people w Diabetes were urinating bunch as in they were losing fluid
•Thomas Willis – Britain ( 1675)- added Mellitus which means Sweet
Macleod and Collin isolated insulin
Insipidus means tasteless
What is diabetes
Explain how it occurs
Diabetes mellitus is heterogenous group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
Or it is a complex chronic metabolic disease and is associated with relative or absolute impaired insulin secretion
Along with varying degrees of peripheral resistance to insulin
So in a normal person, the pancreas produces jnsuoin and this insulin binds to insulin receptors on the cell to allow glucose to enter into the cell
In type 1 diabetes, the pancreas doesn’t produce the insulin in the first place so it can’t bind to the insulin receptors hence it stays outside in the blood.
In type 2, the pancreas produces but the cell doesn’t respond to the insulin produced properly so the insulin is there alright but the glucose is still in the blood.
Name five types of diabetes
How does phaeo cause high bp and dm
How do steroids cause high glucose
How does Cushing syndrome cause dm
ADA classification:
Type 1
•Type 2
•Monogenic diabetes
•LADA
•DM associated with endocrinopathies- acromegaly, cushings, pheo( catecholamines produced too much. Leads to high bp and One of the classical symptoms of pheochromocytoma crisis is hyperglycemia [1] that might be caused by increased insulin resistance in peripheral tissues and impaired insulin secretion [2]. ) ,glucagonoma
•Genetic syndrome- downs , turners syndrome, klienefelters syndrome
•Drug induced eg- steroids or glucocorticoids , post transplant medication, iv pentamidine
•Dx of exocrine pancreas- ca pancreas, pancreatitis, trauma, pancreatectomy, cystic fibrosis
•GESTATIONAL DM
Phaeo:
Catecholamines and a number of other hormones released during stress states contribute to the development of hyperglycemia by directly stimulating glucose production and interfering with tissue disposal of glucose.
Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues.
Norepinephrine (NE) and epinephrine (Epi) help maintain normal blood glucose levels by stimulating glucagon release(Insulin controls whether sugar is used as energy or stored as glycogen. Glucagon signals cells to convert glycogen back into sugar. Glucagon is a glucoregulatory peptide hormone that counteracts the actions of insulin by stimulating hepatic glucose production and thereby increases blood glucose levels.) , glycogenolysis, and food consumption, and by inhibiting insulin release.
Steroids:
How do steroids induce or bring on diabetes? Normally, the liver reduces the amount of glucose it releases in response to insulin. Steroids make the liver less sensitive to insulin so it carries on releasing glucose even if the pancreas is releasing insulin.
Steroids can increase your blood sugar level in different ways. They can:
cause the liver to release more glucose
stop glucose being absorbed from the blood by the muscle and fat cells
reduce the body’s sensitivity to insulin.
All these things can mean too much glucose stays in your blood. This can lead to diabetes.
Cushing’s syndrome is a condition in which can occur if you have high levels of the stress hormone, cortisol, in your blood. Cortisol increases our blood pressure and blood glucose levels and diabetes is one complication which can result from untreated Cushing’s syndrome.
State some characteristics of type 1 DM,which people does it usually occur in,what does it usually present w,state three antibodies that are identified in the blood of someone w type 1 DM
About 5 percent of all diabetics
•X’RISED BY cell mediated AUTOIMMUNE DESTRUCTION OF THE B CELLS
•USUALLY OCCURS IN CHILDREN
•HOWEVER ADULTS CAN ALSO HAVE TYPE 1- LADA
•USUALLY PRESENTS WITH DKA
•AUTOANTIBODIES IDENTIFIED INCLUDE- ICA, GAD65, IA-2A,
Type 1 is insulin dependent
Beta cells produce insulin so if it’s destroyed by antibodies there won’t be enough insulin
Type 1 continued
•Exact cause not known
•Associated with HLA DR/DQ
•MAY BE TRIGGERED BY VIRAL INFECTION
What is LADA and state the full meaning
Not a type of DM on it own
•Category to identify adults with Type 1 diabetes
•Associated with autoantibodies
Latent autoimmune diabetes of adulthood (LADA)
Explain type 2 diabetes
About 90-94% of all diabetics
•X’rised by insulin insensitivity and relative insulin deficiency
•Usually occurs in adults
•However due to childhood obesity, incidence increasing in children
•Usually associated with complications at the time of diagnosis
Name the characteristics of ominus octet
INSULIN RESISTACE IN THE MUSCLES- >POOR GLU UPTAKE
•INSULIN RESISTANCE IN THE LIVE-> OVERPRODUCTION OF GLU
•B CELL FAILURE
•INCREASE LIPOLYSIS
•INCREASE GLUCOSE ABSORPTION BY THE KIDNEYS
•INCRETIN DEFICIENCY/RESISTANCE
•INSULIN RESISTANCE IN THE BRAIN
•ALPHA CELL HYPERPLASIA> HYPERGLUCAGONOMA
State the differences between type 1 and type 2 diabetes
Type 1 the onset is sudden
Type 2 onset is gradual
Type 1 occurs at any age (mostly young people)
Type 2 occurs mostly in adults
Type One occurs in thin or normal people
Type 2 occurs in obese people
Ketoacidosis is common in type 1
It’s rare in type 2
Autoantibodies is usually present in type 1
It’s absent in type 2
Endogenous insulin is low or absent in type 1
It’s normal,decreased or increased in type 2
50percent concordance in identical twins in type 1
90 percent concordance in identical twins in type 2
Type 1 is less prevalent
Type 2 is more prevalent
90percent concordance
State the differences between LADA and type 2 diabetes
LADA-LOWER BMI
Type 2-INCREASED BMI
LADA-USUALLY NOT ASSOCIATED WITH Type 2-METABOLIC SYNDROME
ASSOCIATED WITH METABOLIC SYNDROME
LADA-NOT ASSOCIATED WITH POSITIVE FAMILY HISTORY
Type 2-POSITIVE FAMILY HISTORY
LADA-AGE OF ONSET 30-50YRS
Type 2-AGE OF ONSET >50 YRS
LADA-C- PEPTIC LEVELS ARE LOW
Type2-C- PEPTIDE LEVELS NORMAL OR HIGH
LADA-AUTOANTIBODIES PRESENT
Type2-AUTOANTIBODIES ABSENT
LADA-ASSOCIATED WITH SPECIFIC HLA –HLA DQB1
Type 2-GENETICS IS COMPLEX
State the two types under monogenic diabetes Mellitus
What is monogenic dm
What is MODY
1.Neonatal DM-What Is Neonatal Diabetes? Neonatal diabetes mellitus is a rare form of diabetes that occurs within the first 6 months of life. Our bodies need insulin to help our cells make energy. Infants with this condition do not produce enough insulin, which increases blood glucose levels.
2.MODY
Monogenic diabetes is a rare condition resulting from mutations (changes) in a single gene. In contrast, the most common types of diabetes—type 1 and type 2—are caused by multiple genes (and in type 2 diabetes, lifestyle factors such as obesity).
MODY stands for “Maturity-onset diabetes of the young” and was given that name in the past because it acted more like adult type of diabetes (Type 2 Diabetes) but was found in young people. MODY limits the body’s ability to produce insulin, but is different than the juvenile type of diabetes (Type 1 Diabetes).
Name four Characteristics of MODY
USUALLY OCCUR IN YOUNG INDIVIDUALS/ CHILDREN
•AUTOSOMAL INHERETANCE PATTERN
•MORE THAN 8 GENETIC MUTATIONS IDENTIFIED
•COMMON TYPES- HNF4B, GCK, HNF-1A ETC
•SOME OF THESE INDIVIDUAL ARE SENSITIVE TO SULPHANYLUREAS
Name the complications of DM
•TYPICALLY GROUPED INTO
•MICROVASCULAR COMPLICATIONS (small vessels)eg- nephropathy, retinopathy, NEUROPATHY
•MACROVACULAR COMPLICATIONS eg peripheral artery dx, stroke, myocardial infarction
•RECURRENT INFECTIONS- UTIs , SKIN INFECTIONS( FURUNCULOSIS, CELLULITIS ,FORNIER’S GANGRENE ETC)
If person is getting boils by heart check for diabetes
Hyperglycemia isn’t as dangerous as hypoglycemia but hypo is an emergency
True or false
True
Cortisol pushes sugar into the blood while insulin pushes sugar to the tissues true or false
True
CAUSE OF BLINDNESS IN ADULTS ( 20-70YRS)
•LEADING CAUSE OF NON TRAUMATIC LOWER EXTREMITY AMPUTATION
•ESRD ABOUT 20-30%
In DM true or false
True
What are the typical symptoms of insulin deficiency
Typical symptoms of insulin deficiency- polyuria, polydipsia, polyphagia, weight loss
•Take history of possible complications
How is DM diagnosed
What is the normal ,prediabetic and diabetic values or ranges for RBS,FBS,HbA1C,OGTT
FBS RBS use two or more values to determine if a person has diabetes
If the person has the classical signs of diabetes you can accept a high value of FBS or RBS checked once
FBS
3.9-5.5-normal
≥5.6-<7-prediabetes
>7-diabetes Mellitus
RBS
4-7.8-normal
≥7.8-<11-prediabetes
>11-diabetes Mellitus
OGTT
3.9-5.5-normal
≥7.8-<11-prediabetes
> 11-DM
HBA1C
<5.6-normal
≥5.6-<6.4-prediabetes
>6.5-DM
Name ten tests that are done in DM
FBC •BUE/CR •LFT RFT •HBA1C •UACR •LIPIDS •URINE R/E
- TEST FOR AUTOANTIBODIES-
- ICA- ISLET CELL CYTOPLASMIC ANTIBODIES
- GAD- GLUTAMIC ACID DECARBOXYLASE AUTOANTIBODIES
- INSULIN ANTIBODIES
- IA-2A- INSULINOMA ASSOCIATED-2 AUTOANTIBODIES
C PEPTIDE LEVELS
•GENETIC TESTS FOR SPECIFIC MUTATIONS
How is DM managed,pharmacological,non pharmacological
MULTIDICIPLINARY- •Dietician •Physical Therapist •Nurses •Clinicians •Ophthalmologists •Podiatrists
DRUGS or pharmacological
•ORAL HYPOGLYCEMIA DRUGS
•ORAL HYPOGLYCEMIC AGENTS- BIGUANIDES, TZD, SU, MEGLITINIDE, DPP4 INHIBITORS, GLP 1 AGONISTS, SGLT 2 ANTAGONISTS
•INSULIN-
- CONTROL OF HYPERTENSION
- CONTROL OF LIPID LEVELS
- SCREEN FOR EARLY ONSET OF COMPLICATIONS AND INSTITUTE APPROPRIATE CARE
FBS/GLUCOSE PROFILE •3-4 MONTHLY HBA1C •YEARLY LIPIDS •YEARLY UACR •YEARLY OPHTHOMOLOGIST REVIEW
It’s better to catch diabetes early at the pre diabetic stage true or false
True
Name some complications of diabetes Mellitus
Acute- hypoglycemia, hyperglycemia, hhs, dka
•Chronic- microvascular and macrovascular
What blood glucose value is considered as hypoglycemia
State four causes of hypo
And six symptoms of hypo
Blood glucose < 3.1mmol/l
•Mismatch of carbohydrate availability and hypoglycemic agents
Causes •Overdosage of insulin or hypoglycemic agents •Undereating •Unplanned exercise •Skipping or omitting meals •Stress / overexertion
Symptoms
Sweating •Lightheadedness •Tremors •Palpitations •Irritability/ behavioural changes/confusion •Yawning •Anxiety •Seizures •Comapermanent brain damage death
How is mild hypoglycemia managed
Give simple sugars p.o.(15gm of rapid acting sugar) Examples: -8oz of fruit juice 8oz of skim milk 3glucose tablets 3-4oz of regular soft drinks 3-4pieces of hard candy 1tbsp of sugar 5ml of pure honey
Ask patient to identify cause of hypoglycemia and try to avoid such incidents.
•Should carry fast sugar around
- Nil per os if confused or unconscious
- Should follow up with complex carbohydrate and proteins
15/15 rule
Explain the 15/15 rule
Should check blood sugar levels in 15min, if less than 5mmol/l, should repeat 15mg of sugar until normal levels is attained
•Contact medical care provider if the more than 3 hypoglycemic episodes per week
How is hypoglycemia managed in an unconscious patient
25mls -» of 50% dextrose till the patient is conscious
•Then set up 5% dextrose
Glucagon1mg subq,IM,IV follow with intravenous or oral carbs Action:hormone -raises BS levels Onset of 10 minutes Duration of 25minutes Position -side lying S/E: N/V
How is hypoglycemia considered gerontological
Cognitive defects - not recognize S and S
Decreased renal function-oral hypoglycemic meds stay longer in the body
More likely to skip a meal
Vision problems-inaccurate insulin draws
What are the nursing measures in hypoglycemia
Follow protocol Carry simple sugars at all times S and S or hypoglycemia How to prevent hypoglycemia Check FSBS if you suspect Encourage to wear ID bracelet Teach family that belligerence(hostile attitude and aggressiveness) is a sign of hypoglycemia
What is DKA
Which type does it usually occur in
At what sugar level does it occur at
Serious complication of dm
•Usually occurs usually with type 1 but can also occur with type 2
•Usually occurs at sugars levels above 14mmol/l
What is the physiology of DKA
Three sentences please
Results from breakdown of fat and overproduction of ketones by the liver and loss of bicarbonate
Causes of DKA or etiology
Illness
Infection
Stress(physical or emotional)
Number 1causes are the above
Trauma Surgery Pregnancy Absence or inadequate insulin -taking too little insulin -omitting doses of insulin
A known diabetic that has increased energy needs
Initial or undiagnosed diabetes
Developing insulin resistance
What are the clinical features of DKA
Hyperglycemia
Dehydration
Electrolyte loss
Metabolic acidosis
What is the pathophysiology of DKA
When there isn’t enough insulin glucose stays in the blood and this causes DKA in two mechanisms 1. so muscles don’t get enough energy causing increased fat metabolism leading to increased ketones in the blood causing metabolic acidosis leading to decreased serum pH and increased respiratory rate or 2. Glucose bunch in the blood causes hyperglycemia causing osmotic diuresis (causing electrolyte loss )leading to polyuria (this also causes electrolyte loss) and polydipsia leading to dehydration
What are the signs and symptoms (S and S) of DKA
Hyperglycemia -it increases blood glucose -person gets tired easily Polyphagia Decreased attention,confusion N/V,abdominal pain Blurred vision
Dehydration -polydipsia Polyuria Dry/flushed skin Orthostatic hypotension Tachycardia Headaches Decreased sodium and potassium levels
How is DKA diagnosed using blood and urine
What do you check for in the blood and urine and what are the results to see to diagnose DKA
Blood:
1.Serum osmolality
It is increased
And it’s thick
2.Ketones
They’re positive
3.bicarbonate
It is reduced
It’s less than 15mEq/L
4.pH
It’s reduced
Less than 7.3
5.sugar levels
They’re elevated
Greater than 250 mg/dL
- BUN Blood urea
Nitrate
7.increased
Dehydration
Urine
- ketones are present
- glucose is present
- specific gravity of urine is decreased
How is DKA managed
Focus on the four main clinical features Hyperglycemia Dehydration Electrolyte loss Acidosis
Alterations in blood sugar causes?
How does the blood sugar affect large blood vessels (macro circulation) and small blood vessels(microcirculation)
It causes hyperglycemia and hypoglycemia
Macro-
Atherosclerosis occurs more frequently earlier in diabetics
Involves coronary,peripheral, and cerebral arteries
Micro-
Affects basement membrane of small blood vessels and capillaries
Involves tissues affecting eyes and kidneys
When does HHNK occur (hyperglycemia hyperosmolar nonketonic syndrome)
It occurs in all types of diabetes especially which type
Occurs when there’s insufficient insulin to prevent hyperglycemia but there is enough insulin to prevent ketoacidosis
It occurs in all types of diabetes
Especially type 2
What are the characteristics of HHNKS and what is the difference between it and DKA
Extreme hyperglycemia (800-2000mg/dl) Undetectable ketonuria Absence of acidosis
Major difference from diabetic ketoacidosis is the lack of ketonuria cuz there’s some residual ability to secrete insulin in NIDDM
What are the precipitating factors of HHNKs
Infection (most common) Therapeutic agent or procedure Acute or chronic illness Overeating Stress Too little insulin
Nursing responsibilities in HHNK
It’s the same as DKA Insulin Hydration Electrolyte replacement and monitoring Treat underlying cause
What are the acute complications of DM
Hypoglycemia
DKA
HHNKS
State four macrovascular and microvascular complications ( chronic complications of diabetes)
~~~
Macrovascular ( Post prandial glucose)
-Arteriosclerosis
This is characterized by thickening and loss of elasticity of the arterial walls “hardening of the arteries “
-coronary artery disease( the heart): high blood pressure and insulin resistance and increases risk of coronary heart disease
-cerebrovascular disease( the brain):increased risk of stroke
-peripheral vascular disease ( the peripheries)( narrowing of blood vessels increases risk for reduced blood flow to legs
Microvascular :(Fasting glucose )
- characterized by basement membrane thickening
- affects smallest blood vessels
- due to hyperglycemia
Eye:high blood fluid and high blood pressure damages eye blood vessels causing retinopathy and cataract and glaucoma
Kidney:
High blood pressure damages small blood vessels and excess blood glucose overworks the kidneys resulting in Nephropathy
Nerves:
Hyperglycemia damages nerves in the eprioheral nervous system
Cardiovascular disease is the major source of mortality in patients with type 2 DM true or false
True
Two thirds of people with diabetes due of heart disease or stroke
Men with diabetes face a 2fold increased risk for CHD and women have a 3fold to 4fold increased risk
Diabetics are more likely to develop MI,Congestive Heart failure
True or false
True
How are the complications prevented
Managing diabetes
Lowering risk factors for conditions
Routine screening for complications
Implementing early treatment
What is the physiology of the pancreas (what the pancreas produces and the functions of what is produced
Where is the pancreas located?
The pancreas is a dual-functional gland, with both exocrine (digestive) and endocrine (hormonal) functions.
In this article, we shall look at the endocrine functions of the pancreas and their clinical significance.
Cells of the Pancreas
The pancreas is a partially retroperitoneal, abdominal organ found posterior and inferior to the stomach. Further information on the anatomy of the pancreas can be found here.
There are a variety of cell groups within the pancreas. Firstly, there are clusters of cells known as Islets of Langerhans. These islets contain the cell types that produce the hormones relating to the endocrine functions of the pancreas. There are also acini and duct systems within the pancreas, which are responsible for producing enzymes relating to the exocrine functions of the pancreas.
Islets are thought to make up 5% of the overall volume of the pancreas, although they receive around 15% of its blood flow. The Islets of Langerhans contain the following cell types:
Alpha cells – these make up roughly 15-20% of Islet cells and are responsible for producing glucagon
Beta cells – these make up 65-80% of Islet cells and produce insulin and amylin
Delta cells – these make up 3-10% of Islet cells and produce somatostatin
Gamma cells – these make up 3-5% of Islet cells and are responsible for production of pancreatic polypeptide
Epsilon cells – these make up less than 1% of Islet cells and produce ghrelin
By User:Polarlys (Own work) CC BY 2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons
Fig 1 – The lighter tissue in this section is the Islet cells. The darker staining tissue is pancreatic acini.
Pancreatic Hormones
Pancreatic hormones are produced in the Islets of Langerhans. Scattered throughout exocrine tissue in the tail of the pancreas, these are spherical groups of different cell types producing different polypeptide hormones.
There are 6 key polypeptide hormones secreted by the endocrine pancreas. The table below summarises the cells that produce these and the main functions of these hormones:
1.Pancreatic Hormone 2.Produced by 3.Function
1.Insulin 2.Beta cells 3.Decrease blood glucose levels
1.Amylin 2.Beta cells 3.Slows gastric emptying to prevent spikes in blood glucose levels
1.Glucagon 2.Alpha cells 3.Increase blood glucose levels
1.Somatostatin 2.Delta cells 3.Regulates Islet cell secretion of other hormones
1.Pancreatic Polypeptide 2.Gamma cells 3.GI function
1.Ghrelin 2.Epsilon cells 3.Increase in appetite
These hormones can also regulate the action of other cell types within the Islets.
Insulin stimulates action of beta cells and inhibits alpha cells.
Glucagon stimulates action of alpha cells, which in turn then leads to activation of beta and delta cells
Somatostatin leads to inhibition of both alpha and beta cells.
Clinical Relevance
Type 1 Diabetes Mellitus
Diabetes Mellitus is an endocrine disorder characterised by chronic hyperglycaemia due to either insulin resistance and/or insulin deficiency. Type 1 Diabetes Mellitus mainly affects younger people <30 years
There is absolute insulin deficiency due to autoimmune destruction of pancreatic beta cells. This means that the beta cells are recognised as “foreign” or “non-self” by the body and so are attacked and destroyed by the body’s immune system.
Viral infection in a young person with pre-disposing factors, e.g. family history, is a common trigger. In some cases there is relative insulin deficiency due to defective Beta cells and inadequate insulin secretion or rate of secretion.
Commonly, Type 1 Diabetes Mellitus presents with a classic triad of symptoms: polyuria, polydipsia and weight loss. Due to the lack of insulin being produced by the body in Type 1 Diabetes, patients must be treated with injectable insulin regime.
The average age of diagnosis in the UK is between 10 and 14 years, therefore effective patient education forms an important part of treatment for this disease. It is a lifelong disease which needs tight control of glucose levels and explaining the importance to children and young adults can be challenging.
State ten causes of pancreatitis
Pancreatitis refers to inflammation of the pancreas – this is can be acute or persist over an extended period (chronic pancreatitis). The causes of pancreatitis can be remembered using the mnemonic – GET SMASHED:
Gall stones
Ethanol
Trauma
Steroids
Mumps
Autoimmune
Scorpion stings
Hypertriglyceridemia, hypercalcaemia and hyperparathyroidism
ERCP – endoscopic retrograde cholangiopancreatography
Drugs – such as sodium valproate, azathioprine and sulphonamides
Pancreatitis creates severe epigastric pain which often radiates to the back, nausea, vomiting and diarrhoea.
Treatment involves supportive measures such as IV fluids and analgesia. Antibiotics are rarely required, as most cases are not due to infection. The underlying cause will then also need to be treated.
What is the anatomy of the pancreas
Anatomical Position
The pancreas is an oblong-shaped organ positioned at the level of the transpyloric plane (L1). With the exception of the tail of the pancreas, it is a retroperitoneal organ, located deep within the upper abdomen in the epigastrium and left hypochondrium regions.
Within the abdomen, the pancreas has direct anatomical relations to several structures
Organs:
Stomach – Separated from the pancreas by the lesser sac, the stomach and pylorus lie anterior and to the pancreas.
Duodenum – The “C” shaped duodenum curves around and outlines the head of the pancreas. The first part of the duodenum lies anteriorly whereas the second part of the duodenum including the ampulla of Vater lies laterally to the right of the pancreatic head
Transverse mesocolon – Attaches to the anterior surface of the pancreas
Common bile duct – Descends behind the head of the pancreas before opening into the second part of the duodenum alongside the major pancreatic duct through the major duodenal papilla
Spleen – located posteriorly and laterally. The lienorenal ligament is formed from peritoneum and connects the spleen to the tail of the pancreas.
Vessels
The pancreas lies near several major vessels and significant landmarks in vascular anatomy:
The aorta and inferior vena cava pass posteriorly to the head of the pancreas.
The superior mesenteric artery lies behind the neck of the pancreas and anterior to the uncinate process.
Posterior to the neck of the pancreas, the splenic and superior mesenteric veins unite to form the hepatic portal vein.
As it journeys from its origin at the celiac plexus to the splenic hilum, the splenic artery traverses the superior border of the pancreas.
By TeachMeSeries Ltd (2023)
Fig 1 – Anterior view of the abdomen. The stomach, transverse colon, and the majority of the small intestine have been removed to expose the underlying pancreas
Anatomical Structure
The pancreas is typically divided into five parts:
Head – the widest part of the pancreas. It lies within the C-shaped curve created by the duodenum and is connected to it by connective tissue.
Uncinate process – a projection arising from the lower part of the head and extending medially to lie beneath the body of the pancreas. It lies posterior to the superior mesenteric vessels.
Neck – located between the head and the body of the pancreas. It overlies the superior mesenteric vessels which form a groove in its posterior aspect.
Body – centrally located, crossing the midline of the human body to lie behind the stomach and to the left of the superior mesenteric vessels.
Tail – the left end of the pancreas that lies within close proximity to the hilum of the spleen. It is contained within the splenorenal ligament with the splenic vessels. This is the only part of the pancreas that is intraperitoneal.
By TeachMeSeries Ltd (2023)
Fig 2 – The parts of the pancreas
Duct System
The exocrine pancreas is classified as a lobulated, serous gland which produces digestive enzyme precursors. It is composed of approximately one million ‘berry-like’ clusters of cells called acini, connected by short intercalated ducts.
The intercalated ducts unite with those draining adjacent lobules and drain into a network of intralobular collecting ducts, which in turn drain into the main pancreatic duct.
The pancreatic duct runs the length of the pancreas and unites with the common bile duct, forming the hepatopancreatic ampulla of Vater. This structure then opens into the duodenum via the major duodenal papilla.
Secretions into the duodenum are controlled by a muscular valve – the sphincter of Oddi. It surrounds the ampulla of Vater, acting as a valve.
By TeachMeSeries Ltd (2023)
Fig 3 – The exocrine pancreas, secreting into the duodenum
Vasculature
The pancreas is supplied by the pancreatic branches of the splenic artery. The head is additionally supplied by the superior and inferior pancreaticoduodenal arteries which are branches of the gastroduodenal (from coeliac trunk) and superior mesenteric arteries, respectively.
Venous drainage of the head of the pancreas is into the superior mesenteric branches of the hepatic portal vein. The pancreatic veins draining the rest of the pancreas do so via the splenic vein.
By TeachMeSeries Ltd (2023)
Fig 4 – The arterial supply and venous drainage of the pancreas
Lymphatics
The pancreas is drained by lymphatic vessels that follow the arterial supply. They empty into the pancreaticosplenal nodes and the pyloric nodes, which in turn drain into the superior mesenteric and coeliac lymph nodes
How is MODY diagnosed?
For patients with diabetes diagnosed before 25years,
1. First check if it was diagnosed before 6 months
If yes, do a genetic test for neonatal diabetes cuz there’s a likelihood that it’s a possible neonatal diabetes
- Was there abrupt onset of ketoacidosis? While the patient is not obese? While that patient has insulin deficiency?
If yes,check for beta cell autoantibodies
If the antibodies are positive, there’s a possible type 1 diabetes
If no, it’s Yong onset diabetes in at least the second generation - Is there obesity? Is there insulin resistance? Are there negative beta autoantibodies ?
If yes, it’s a possible type 2 diabetes
If no, there is negative beta cell autoantibodies and it’s Yong onset diabetes in at least the second generation
Do genetic testing for MODY
IF POSITIVE, it’s a possible MODY
Explain the ominous octet of diabetes mellitus
Type 2 diabetes is characterized by multiple pathophysiologic abnormalities which collectively have been referred to as the Ominous Octet
The Ominous Octet of obesity is an organ-system based rubric, which helps in identification of various sites of dysfunction in a person living with obesity.
Ominous Octet:( all these cause hyperglycemia)
1. Impaired peripheral glucose uptake from the muscles-the receptors on your liver and muscle cells do not function properly to take up glucose, causing glucose to remain in the bloodstream
2.Increased glucose reabsorption by the kidneys-in an attempt to conserve glucose as an energy source, the kidneys hold onto more of it which keeps blood levels high
3.increased lipolysis by fatty tissue and insulin resistance -increased fat breakdown raises triglycerides in the blood which can impair insulin secretion
4.Decreased incretin effect in intestines-gut hormones that normally stimulate insulin secretion in response to food are less effective and produced at lower quantities
5.Impaired insulin secretion by pancreas
6.increased glucagon secretion by pancreas-higher levels of glucagon (a hormone) trigger the production of glucose (sugar)
7. Increased hepatic glucose production by liver -your liver dumps out too much glucose (sugar)
8.neurotransmitter dysfunction by brain-altered neurotransmitter function in your brain which does not properly trigger the sensation of feeling full (appetite)
.
How is DM diagnosed
How is impaired glucose tolerance diagnosed?
How is impaired fasting glucose diagnosed?
Diabetes:
Fasting plasma glucose- more than or equal to 7.0mmol/L or 126mg/dL
Or two hour plasma glucose after 75g anhydrous oral glucose load dissolved in water (OGTT) more than or equal to 11.1 mmol/L or 200mg/dL
Or HbA1C more than or equal to 48mmol/mol equivalent to 6.5%
Or random plasma glucose in the presence of hyperglycemia and more than 11.1 mmol/mol or 200mg/dL
Impaired glucose tolerance diagnosed:
For it to be diagnosed, two of the criteria must be met:
a. Fasting plasma glucose Less than 7mmol/L and
b. two hour plasma glucose after 75g oral glucose load (OGTT) less than 11.1 mmol/L and more than or equal to 7.8mmol/L
Or 140-200mg/dL
How is impaired fasting glucose diagnosed-
Should be diagnosed if the first or both are met:
Fasting plasma glucose 6.1-6.9 mmol/L (110-125mg/dL) and
b. two hour plasma glucose after 75g oral glucose load (OGTT) less than 7.8 mmol/L
Or 140mg/dL
Explain how glycated haemoglobin is formed
How many days does a red blood cell live in the blood
Where is hemoglobin found?
In adults, how many forms of Hb exist and name them and which is more predominant
120days
Hb is found in the blood cell
Glucose or sugar enters in the bloodstream and into the rbc
It binds to the Hb in the rbc
This binding creates glycated hemoglobin
Forms of Hb: Hb A1, Hb A2, Hb F
Hb A1 is predominant
Glycated hemoglobin means a chemically stable conjugate of any of the forms of Hb with glucose
Glycated forms of hemoglobin are formed slowly irreversibly and non enzymatically at a rate that is proportional to the concentration of glucose in the blood
State. glycated haemoglobin pros and cons
Pros:
Chronic hyperglycemia is caught more accurately by HbA1C than FPG
Fasting is not needed for A1C assessment
No acute perturbation (smoking, stress, diet, exercise) affect A1C
Individual susceptibility to protein glycation might be A1C
A1C can be used concomitantly for diagnosing and initiating monitoring of diabetes
Cos:
Diabetes is clinically defined as elevated blood glucose and not elevated glycated proteins
2hours level glucose and Impaired glucose tolerance are stronger than A1C
Standardization of A1C assay is poor compare to glucose assay
A1C of 6.0-6.5% do not predict diabetes as accurately as fasting plasma glucose and 2hour plasma glucose (OGTT)
A1 levels vary not only according to glycemia but also according to erythrocyte turnover rates( examples are hemoglobiopathies , malaria, blood loss)
A1C varies in ethnic groups
Explain four conditions that affect HbA1C ( whether they falsely lower or falsely increase it and why) ?
Erythrocyte lifespan(factor)
Falsely lower- decrease erythrocyte lifespan ( splenomegaly, recent blood transfusion, hemolytic anemia)
Falsely increase- increased erythrocyte lifespan ( splenectomy)
Erythropoiesis:
Falsely lower(reticulocytosis , erythropoietin administration)
Falsely increase(Iron/B12 deficiency ,decreased erythropoiesis
Assay interference:
Falsely elevated- chronic alcoholism
Falsely decreased-severe hypertriglyceridemia
Glycation-
Falsely lowered: high dose vitamin C or E
Falsely elevated : chronic kidney disease
How is the 2 hour post pea dial glucose performed
2 hour plasma glucose- fasts for two hours
Blood is taken
After five minutes , they take glucose preparation
One hour after drinking they take blood sugar
Two hours after drinking. They take blood sugar
What are the stages of diabetic retinopathy
Mild non proliferative DR
Moderat en hon proliferative
Severe non proliferative
Proliferative DR
All these can lead to vitreous haemorrhage and traction retinal detachment and macular edema
In non proliferative DR, there is haemorrhage, hard exudates,aneurysm and in proliferative DR, there are abnormal blood vessels
How does painless and then painful diabetic neuropathy occur
State the risk factors associated wi tbh developing painful neuropathy
DM with hyperglycemia, dyslipidemia and altered insulin signaling can cause microvascular and metabolic changes.
Microvascular chnages lead to reduced perfusion and nerve ischaemia. This leads to structural and functional alterations of peripheral nerves thus leading to painless diabetic neuropathy
The metabolic CHanges lead to hyperactivity of several pathways such as 1. polyol pathway, the polyol pathway activation could be the primary cause of oxidative stress associated with diabetes. However, oxidative stress could be also initiated by autoxidation of glucose and their metabolites, 2.increased intracellular formation of AGEs, increased expression of the receptor for AGEs and its activating ligands, altered mitochondrial function, activation of 3.PKC isoforms and overactivity of the 4.hexosamine pathway.
All these pathways lead to oxidative stress, mitochondrial dysfunction and inflammation. These three also lead to
structural and functional alterations of peripheral nerves thus leading to painful diabetic neuropathy.
Risk factors for developing painful neuropathy include:
Obesity, female gender, genotype and glycemic burden
Other factors include reduced vitamin D,reduced blood flow
Explain the Wagner classification of diabetic foot ulcers
Grade 0- no ulcer in a high risk foot
1- superficial ulcer involving the full skin thickness but not the underlying tissues
2-deep ulcer penetrating down to the muscles and ligaments but no bone involvement or abscess formation
3-deep ulcer with cellulitis or abscess Formation often with osteomyelitis
4- localized gangrene
5-extensive gangrene involving the whole foot
Explain in simple terms diabetic Nephropathy
Poor glycemic control leads to increased blood pressure, increased blood volume and increased renal perfusion
This causes initial increased GFR which causes stress to the glomerulus and leads to pressure induced damage
This leads to podocyte injury and makes the glomerular basement membrane to be permeable to proteins leading to albuminuria
This leads to protein endocytosis into tubular cells leading to inflammation
This leads to tubular fibrosis leading to scarred glomeruli which are not able to filter blood properly anymore
Leading to reduced GFR and diabetic Nephropathy
Generally, how is diabetes managed
1.control fasting and postprandial sugars
2.reach targets HbA1C , Lipids and BP
3.avoid weight gain
4. Treat macro and micro complications and non vascular complications
How often do you screen for the following complications in diabetes
Retinopathy, diabetic neuropathy, Nephropathy, lipids, HbA1C,CAD
Screen for retinopathy- do a dilated eye examination annually
Examination of the feet-inspect feet at each visit and do thorough feet examination annually
Monitor HbA1C every three months until you reach the target you want
Monitor every six months after you reach the target
Measure fasting lipids annually
Measure urine albumin-to creatinine ratio annually
Do additional screening for Coronary artery disease (BP check, smoking history and exercise history) at each visit
For each ominous octet(do for the muscles, kidney and lipolysis) , state the drugs used to treat it and how they work
Ominous Octet:( all these cause hyperglycemia)
1. Impaired peripheral glucose uptake from the muscles-the receptors on your liver and muscle cells do not function properly to take up glucose, causing glucose to remain in the bloodstream
a.Metformin-increases uptake of glucose by liver and muscles and counters insulin resistance
b.insulin-increases uptake of glucose by liver and muscles and storage and metabolism by liver, suppresses glucose production and decreases lipolysis
c.thiazolidinediones (pioglitazone,rosiglitazone)- increases insulin sensitivity
2.Increased glucose reabsorption by the kidneys-in an attempt to conserve glucose as an energy source, the kidneys hold onto more of it which keeps blood levels high
a.SGLT2 (sodium glucose cotransporter 2) inhibitors (canagliflozin, dapagliflozin, and empagliflozin.)-preventing the kidneys from reabsorbing glucose back into the blood. This allows the kidneys to lower blood glucose levels and the excess glucose in the blood is removed from the body via urine.
3.increased lipolysis by fatty tissue and insulin resistance -increased fat breakdown raises triglycerides in the blood which can impair insulin secretion and increase risk of atherosclerosis
a. thiazolidinediones (pioglitazone,rosiglitazone)- increases insulin sensitivity because
Insulin promotes lipogenesis, thereby resulting in the storage of triglycerides in adipocytes and of low-density lipoproteins (LDL) in hepatocytes. Insulin favours the storage of fat in adipose tissue by 3 mechanisms: — 1. it inhibits lipolysis; — 2. increases the glucose uptake, lipogenesis and reësterification of free fatty acids; — 3.
For each ominous octet(do for thepancreas’s ,intestines, liver and brain and) , state the drugs used to treat it and how they work
4.Decreased incretin effect in intestines-gut hormones that normally stimulate insulin secretion in response to food are less effective and produced at lower quantities. Incretins are gut-derived hormones, members of the glucagon superfamily, released in response to nutrient ingestion, mainly glucose and fat. They stimulate pancreatic insulin secretion. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are the two most important hormones
By stimulating insulin secretion in a glucose-dependent manner, they ensure that postprandial glucose levels do not increase excessively.
a. Metformin- increase glucose uptake and counters insulin resitance
b. Colesevelam-Colesevelam, a bile-acid sequestrant, lowers glucose levels in patients with type 2 diabetes mellitus (T2DM) by a mechanism that is associated with increased incretin secretion and improved β-cell function, but not with reduced gluconeogenesis or glucose absorption.
c.alpha glucosidase inhibitors-Alpha-glucosidase inhibitors are antihyperglycemic agents that lower blood glucose by delaying the digestion and absorption of complex carbohydrates. Alpha-glucosidase inhibitors (AGIs; acarbose, miglitol, voglibose). AGIs delay the absorption of carbohydrates from the small intestine and thus have a lowering effect on postprandial blood glucose and insulin levels
5.Impaired insulin secretion by pancreas-
a.Sulfonylurea(Glimepiride,Glyburide
Glipizide ) -stimulate insulin secretion
b.meglitinide:stimulate insulin secretion (There are three available drugs: repaglinide, nateglinide, and mitiglinide.)
c.GLP-1 receptor agonist:increase incretin effect. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses. Examples ;Dulaglutide
Exenatide extended release
Exenatide
Semaglutide
Liraglutide
Lixisenatide
Semaglutide
d. DPP-4 inhibitors:increase incretin effect. DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin. sitagliptin, saxagliptin, linagliptin, and alogliptin
6.increased glucagon secretion by pancreas-higher levels of glucagon (a hormone) trigger the production of glucose (sugar)
a.GLP-1 receptor agonist:increase incretin effect. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses. Examples ;Dulaglutide
Exenatide extended release
Exenatide
Semaglutide
Liraglutide
Lixisenatide
Semaglutide
b.DPP-4 inhibitors:increase incretin effect. DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin. sitagliptin, saxagliptin, linagliptin, and alogliptin
c. Amylin-In the pancreas, amylin inhibits the release of glucagon and thus decreases blood glucose via inhibition of hepatic glucose production.
- Increased hepatic glucose production by liver -your liver dumps out too much glucose (sugar)
Metformin-increases uptake of glucose by liver and muscles and counters insulin resistance
b.insulin-increases uptake of glucose by liver and muscles and storage and metabolism by liver, suppresses glucose production and decreases lipolysis
c.thiazolidinediones (pioglitazone,rosiglitazone)- increases insulin sensitivity
8.neurotransmitter dysfunction by brain-altered neurotransmitter function in your brain which does not properly trigger the sensation of feeling full (appetite)
a. Amylin-In the pancreas, amylin inhibits the release of glucagon and thus decreases blood glucose via inhibition of hepatic glucose production. Example pramlintide is an amylin analogue
b. GLP-1 receptor agonist:increase incretin effect. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses. Examples ;Dulaglutide
Exenatide extended release
Exenatide
Semaglutide
Liraglutide
Lixisenatide
Semaglutide
c. Bromocriptine is thought to act on the circadian neuronal activities in the hypothalamus, to reset an abnormally elevated hypothalamic drive for increased plasma glucose, free fatty acids, and triglycerides in insulin-resistant patients.it is a dopamine receptor agonist
How is type 2 diabetes managed (5 steps)
Why won’t you add insulin to a SU drug
- Get diabetes education,monitor blood glucose and make the lifestyle changes
2.Add a medicine:metformin or blood glucose normalizing medicine - After 3-6 months if patient is not doing well on metformin, add either insulin or another oral medication
Step4. If still, add another oral med or insulin
Step5 : If patient is on three oral meds but still nothing is helping , consider insulin intensified therapy with or without the previous oral meds
No insulin to an SU cuz it can cause hypoglycemia
So in a patient with cost being an issue and without established CKD or ASCVD, what drugs do you give and what to do you give if they’re not working
First give SU or give a TZD
If the SU isn’t working then you switch to a TZD
If you started with a TZD and it’s not work then switch to an SU
If after switching neither is working then switch to low cost insulin
Or DPP-4 inhibitors or SGLT2 inhibitors
So in a patient with cost not being an issue and with established CKD orHF, what drugs do you give and what to do you give if they’re not working
Why would you Avoid TZD in the setting of HF
Start SGLT2 inhibitors with evidence of reducing HF and or CKD progression of eGFR is adequate
If SGLT2 inhibitors are not tolerated or are contraindicated or if eGFR loss is less than adequate then add GLP-1 agonist
Avoid TZD in the setting of HF
However,TZDs increase renal sodium and water reabsorption, leading to fluid retention and overt signs of HF in patients with diabetes.
So in a patient with cost not being an issue and with established CKD orHF, what drugs do you give and what to do you give if they’re not working
Why would you Avoid TZD in the setting of HF
Start SGLT2 inhibitors with evidence of reducing HF and or CKD progression of eGFR is adequate
If SGLT2 inhibitors are not tolerated or are contraindicated or if eGFR loss is less than adequate then add GLP-1 agonist
Avoid TZD in the setting of HF
However,TZDs increase renal sodium and water reabsorption, leading to fluid retention and overt signs of HF in patients with diabetes.
For diabetic combinations, which of the following drugs can be added to it to make a triple therapy combo
SGLT2i ,DPP-4 inhibitor,GLP-1 agonist, TZD,SU
For Metformin + SU, you can give all the drugs except adding another SU
Metformin + SGLT2 i, you can give all except SGLT2 i
Metformin + DPP-4 i, you can give all except DPP-4 i and GLP-1 agonist
Metformin + GLP-1 agonist, you can give all except GLP-1 agonist and DPP-4 i
Metformin + TZD, you can give all except TZD
Metformin + basal ( not intensive) insulin , you can give all except SU
Name the types of mixture and when they are given
Fast acting (soluble) and long acting (isophane) insulin
Mixtard is a suspension for injection that contains
Mixtard is given 30mins before meals
Mixtard 30: soluble insulin 30% and isophane 70%
Mixtard 40: soluble insulin 40% and isophane 60%
Mixtard 50: soluble insulin 50% and isophane 50%
