Module 2 Flashcards
(139 cards)
1
Q
main complications of diabetes:
A
microvascular disease
macrovascular disease
2
Q
Microvascular Disease
A
nervous system—causing neuropathy
eyes—causing retinopathy (both non-proliferative and proliferative)
kidneys—causing nephropathy
3
Q
Retinopathy
A
Diabetes is the leading cause of blindness
35% of people with diabetes had
7% had proliferative diabetes retinopathy
7% had diabetic macular oedema
10% vision-threatening stages
4
Q
Modifiable Risk Factors for T2DM
A
hyperglycemia
hypertension
dyslipidemia
5
Q
Macrovascular Complications
A
heart disease, stroke and peripheral arterial disease.
6
Q
Atherosclerotic cardiovascular disease (ASCVD)—defined as
A
coronary heart disease (CHD), cerebrovascular disease, or peripheral arterial disease presumed to be of atherosclerotic origin—is the leading cause of morbidity and mortality for individuals with diabetes.
7
Q
younger onset TDM compared to older age onset
A
increase in microvascular and macrovascular complications
more rapid progression
worse prognosis
8
Q
What should women with diabetes (either type 1 or 2) do to reduce the risks to their unborn child during pregnancy?
A
should have excellent glycaemic control - an HbA1c level of <6.5% (48 mmol/mol),reduce the risk of congenital anomalies
pregnancy should be avoided at HbA1c >10% (86mmol/mol).
take folic acid 5mg daily starting pre-conception and continue until 12 weeks gestation
low-dose aspirin from the end of the first trimester to delivery to reduce the risk of pre-eclampsia.
9
Q
What are the congenital abnormalities that can occur?
A
diabetic embryopathy : anencephaly, microcephaly, congenital heart disease, and caudal regression
directly proportional to elevations in A1c during the first 10 weeks of pregnancy
10
Q
What complications can arise with gestational diabetes?
A
Gestational diabetes, develops in the third trimester
risk of macrosomia and birth complications.
11
Q
Is there a risk to the child after they are born?
A
increased risk of type 2 diabetes and obesity for the child later in life.
12
Q
How Do We Treat Diabetes?
A
life styles changes, weight loss and increased activity
glycemic control
the management of hypertension and dyslipidemia
good nutrition
13
Q
Goals of Medical Nutritional Therapy
A
1] Promote and support healthful eating patterns, including a variety of foods, in appropriate portions, to:
Improve individualised HbA1c, BP and cholesterol levels
Achieve and maintain body weight goals
Delay or prevent complications
2] Address individual nutrition needs based on personal and cultural preferences. Consider:
Health literacy and numeracy
Access to food choices
Willingness to make behavioural changes and barriers to change
3]Encourage people to maintain the pleasure of eating
Provide positive messages about food choices
Limit food choices only where indicated by evidence
4]Provide the person with diabetes with practical tools for day-to-day meal planning
14
Q
Diabetes Remission
A
some groups with T2DM have demonstrated a return to normal glycaemia following weight loss.
15
Q
What is the DiRECT study?
Who participated?
What are some implications of the study?
What were the findings of the study?
A
The Diabetes Remission Clinical Trial (DiRECT)
primary care led weight management programme aiming to help people with T2DM of less than 6 years’ duration to lose 10-15kg.
306 people aged 20-65 with T2DM and BMI 27-45kg/m2
intervention group received liquid meal replacement [The Counterweight Plus very low calorie liquid meal]supplements providing 825-853 kcal/day for 12 to 20 weeks with a weight loss goal of 15kg before food was gradually reintroduced
Diabetes and blood pressure drugs were stopped
Remission was achieved in around 50% of participants
Decreases in liver and pancreas fat were identified on scanning
thought to have contributed to improved beta cell function and glycaemic control
16
Q
Older People and Anorexia
A
lower energy needs,suffer from lack of appetite, altered taste and smell, and difficulties with chewing and eating,impact on their willingness and ability to eat.
result in anorexia with or without micro nutrient deficiencies.
intentional and un-intentional weight loss risk to bone density and the potential of micro nutrient deficiency
17
Q
Older People and Obesity
A
Changes in muscle mass and strength in the elderly (sarcopenia)
BMI is not a good predictor of adiposity.
18
Q
Chronic Care Model (CCM)
A
multi-faceted approach
improving the skills of health care professions
working in teams
strategies to educate and support patients
health information systems (including local registers)
decision support mechanisms
19
Q
CCM Element
A
Self-management support =Empower and prepare patients to manage their health and health care
Delivery system—a multi-disciplinary team= Assure the delivery of effective, efficient clinical care and self-management support
Decision support= Promote clinical care that is consistent with scientific evidence and patient preferences
Clinical information systems=Organize patient and population data to facilitate efficient and effective care
Health care organization=Create a culture, organization and mechanisms that promote safe, high quality care.
Community resources=Help patients access needed services in the community.
20
Q
Team Members of Diabetic Care
A
Doctors and nurses Dietitian Administrator Health educator Pharmacist Podiatrist Mental Health Worker
21
Q
Care Coordinator
A
Form a pro-active working relationship Carry out a person centered assessment Provide a central, continuous point of contact act as the key advocate Assist the patient Demonstrate local knowledge Carry out care planning Hold people to account
22
Q
Different Modes of Care
A
Delivering Care
Structured Education Programs
23
Q
why UKPDS was a landmark clinical trial?
A
involved people who were newly diagnosed and without complications.
treat early
24
Q
Metformin
A
Gluconeogenesis is the process by which glucose is generated from non-carbohydrate precursors.
Metformin acts to inhibit this process in the liver,
through inhibition of the mitochondrial respiratory chain complex 1 and activation of AMP-activated protein kinase.
increases the peripheral utilization of glucose in the tissues
decreases absorption from the gastrointestinal tract
cheap to use and does not cause hypoglycemia.
a long-term reduction in risk of microvascular complications, myocardial infarction and overall mortality.
‘start low, go slow’ titration
Gut symptoms not tolerated, changing to a slow-release version of the drug or possibly by decreasing the dose.
can be used in pregnancy for either pre-existing or gestational diabetes.
Long-term metformin result in vitamin B12 -deficiency - test and supplement in those with anaemia or neuropathy.
25
Sulfonylureas
closing ATP-sensitive potassium channels in the beta-cell of the pancreas.
initiates a chain of events - results in insulin release.
26
meglitinides
stimulate the release of insulin from the pancreatic beta cells by binding to ATP sensitive potassium channels.
27
Thiazolidinediones
binding to peroxisome proliferator-activated receptors (PPARs) changing the transcription of genes
influence lipid and carbohydrate metabolism.
first drug[troglitazone] launched in 1997 withdrawn after cases of hepatotoxicity and liver failure.
Pioglitazone is the only drug still available
28
alpha glucosidases inhibitor
delays the digestion and absorption of starch and sucrose by inhibiting intestinal alpha glucosidases.
29
GLP1 receptor agonists
also called incretin mimetics
help to lower blood sugar levels after a meal.
given by daily or weekly injection,
oral versions are in late stage development.
30
Dipeptidyl peptidase 4 (DPP-4) inhibitor
DPP-4) is an enzyme = cleave the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), thus inactivating them
results in increased blood concentration of these incretins
augment the glucose-dependent insulin and glucagon responses
reducing blood sugar.
31
Sodium-glucose co-transporter-2 inhibitor [SGLT2] inhibitor
Sodium-glucose co-transporter-2 is a sodium dependent glucose transport protein
inhibition causes less glucose to be reabsorbed from the urine
decreasing blood sugar levels.
32
What is the most serious potential complication of metformin use?
What co-morbidities or other medical events make it more likely?
Lactic acidosis
mortality rate of around 50% ,less than 10 cases per 100,000 patient years of use.
Triggers for lactic acidosis include: Triggers dehydration and sepsi
metformin should be stopped during acute illness where tissue hypoperfusion or dehydration are likely to occur (e.g. myocardial infarction or gastroenteritis).
stopped for two days before having a general anesthetic
three days after the use of iodine containing contrast media.
should not be used at all if -
creatinine is over 1.70 mg/dL (150 µmol/L)
eGFR less than 30 mL/min/1.73 m2
reviewed when the creatinine reaches 1.47 mg/dL (130 µmol/L)
eGFR falls below 45 mL/min/1.73 m2.
eGFR falls to between 30 and 45 mL/min/1.73 m2,dose is reduced by half to maximum 1g daily
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two different types of Metformin that can be administered.
Metformin standard release
500mg with breakfast
Increase to twice daily
then three times daily at one week intervals for a normal maintenance dose of 2g per day
usually 1g twice daily, although 850mg three times daily can be used
Adhere to the 3g daily maximum limit
Metformin prolonged release (or modified release)
500mg with evening meal
Gradually increase dose every 10–15 days for a normal maintenance dose of 2g per day
Adhere to the 2g once daily maximum dose limit
34
Different HbA1c Targets
1]patients without significant hypoglycemia or other adverse effects, newly diagnosed, treated only with lifestyle change or metformin, have a long life expectancy and no significant cardiovascular disease.
2]Most adults who aren’t pregnant should achieve this HbA1c target.
3]Patients with a history of symptomatic hypoglycemia, limited life expectancy, advanced micro- or macro-vascular complications or extensive co-morbidities. Long-standing diabetics who have always struggled to maintain control despite education and appropriate management might also fit into this group.
1]6.5% (48 mmol/mol)
2]7% (53 mmol/mol)
3] 8% ( 64mmol/mol)
35
which therapies would you discuss as follow-on to metformin?
DPP4-I [weight neutral]
SGLT2-I[promote weight loss]
GLP1 rA[costly]
priority is to avoid further weight gain and ideally to lose weight.
consider an SGLT2 inhibitor before a GLP-1 RA if the eGFR is above the threshold for initiation of this class of drugs (currently eGFR 60 mL/min/1.73 m2)
36
Sulfonylureas
Examples?
MOA?
Guideline Recommendition?
gliclazide, glimepiride, glibenclamide (glyburide)
only works if there are functioning beta cells
closing ATP-sensitive potassium channels in the beta-cell of the pancreas. This initiates a chain of events which results in insulin release
cheap
most common side effect is hypoglycaemia
recommending gliclazide as a specific drug
in terms of hypoglycaemia risk, gliclazide is a safer option than glibenclamide (glyburide)
used with care in patients with renal impairment.
neutral with atherosclerotic cardiovascular disease and heart failure.
37
three different types of sulfonylureas
Gliclazide immediate release
- 40-80mg daily with breakfast
- give in divided doses when dose is above 160mg daily
- 320mg daily maximum limit
Gliclazide slow release
- 30mg daily with breakfast
- 120mg daily maximum limit
- 30mg modified release gliclazide = 80mg standard release
Glimepiride
- start with 1mg daily
- increase at 1-2 week intervals by 1mg to usual dose of 4mg daily
- 6mg maximum dose
- little additional benefit above 4mg
38
Thiazolidinediones
Examples?
MOA?
why controversial?
pioglitazone, rosiglitazone
binding to peroxisome proliferator-activated receptors (PPARs) and changing the transcription of genes that influence lipid and carbohydrate metabolism
actions at PPAR gamma 1 and 2 (found mainly in adipose tissue) improve the insulin sensitivity of the peripheral tissues
action at PPAR alpha affects lipid metabolism
overall effect = increase glucose uptake and use in peripheral tissues and decrease gluconeogenesis in the liver reducing insulin resistance
troglitazone(1997): hepatotoxicity and liver failure.
rosiglitazone(1999): withdrawn from UK in 2010
increased risk of heart failure
Pioglitazone benefit for atherosclerotic CVD provided they do not have a history of heart failure.
39
Thiazolidinediones Risk
eye- Worsening of macular oedema
heart- increased risk for patients with heart failure when it is combined with insulin.
lungs- very small increase in pneumonia with pioglitazone
bladder-small increased risk of bladder cancer
should not be used in patients with a history of bladder cancer or uninvestigated macroscopic hematuria,those who have risk factors for bladder cancer
bones- increased risk of fractures.Postmenopausal women are most at risk.
40
Thiazolidinediones—Dose Information
pioglitazone
15–30 mg once daily (15mg if elderly)
45mg daily maximum limit
41
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Alpha Glucosidase Inhibitors
Examples?
MOA?
Side effects?
Guideline Recommendition?
```
acarbose and miglitol
delays the digestion and absorption of starch and sucrose by inhibiting intestinal alpha glucosidases.
Low risk for hypoglycaemia, decreased postprandial glucose rises, cardiovascular safety and low cost
carbohydrates remain in the intestine, causing side effects : flatulence and diarrhea
relatively modest effect on HbA1c
taken three times a day (with each meal)
42
Polysaccharides
polysaccharides will not help to reverse the hypoglycaemia in the event of a hypoglycaemic episode absorption will be blocked by the drug
only glucose tablets (monosaccharaide )are used to treat hypoglycaemia in patients taking alpha glucosidase inhibitors.
43
Alpha Glucosidase Inhibitors – Dose Information
acarbose
50mg daily
Increase to 50mg three times a day for 6–8 weeks, to 100mg three times a day
200mg, three times a day, daily maximum limit
modest reduction in HbA1c
GI A/E
3 times daily
not widely use
44
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Meglitinides
Examples?
MOA?
Side effects?
Guideline Recommendition?
```
nateglinide and repaglinide.
stimulate the release of insulin from the pancreatic beta cells by binding to ATP sensitive potassium channels.
their affinity to the binding site is lower and they dissociate from it more quickly than sulfonylureas
much quicker acting than the sulfonylureas
Normal action is within 15–30 minutes.
taken immediately before a meal,
titrated towards the number of meals missed.
cause hypoglycaemia and weight gain
relatively cheap, reduce post prandial glucose increases and are safe when used cautiously in renal disease.
45
Meglitinides – Dose Information
Repaglinide
0.5mg within 30 minutes of a main meal or 1mg if changing from another oral antidiabetic drug
Adjust at intervals of 1–2 weeks
16mg daily maximum limit
Nateglinide
60mg three times a day, taken within 30 minutes of a main meal
180mg, three times a day, maximum limit
not use widely
useful for irregular eating pattern
46
GLP-1 Receptor Agonists (GLP-1 RAs)
Incretin Mimetics
1]What is GLP-1?
2]How long does the normal incretin response last?
3]What are examples of GLP-1 RA drugs?
4]How do they work?
5What are the advantages of this treatment?
6]Expense and side effects?
7]What do the guidelines recommend?
1]Glucagon-like peptide 1,one of the main incretin hormones
increases glucose dependent insulin secretion and decreases glucagon secretion
slows gastric emptying
increases satiety
2]response lasts for 2–3 hours after a meal is eaten.
3]exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide
4]GLP-1 is inactivated by dipeptidyl peptidase 4 (DPP-4),any synthetic GLP-1 RAs need to be resistant to this inactivation
molecular manipulation,addition of extra fatty acids.
extra C-16 fatty acid makes liraglutide resistant to DPP-4,gives it a longer half-life.
5]decreased weight,reduced glucose,proven CVD benefits (liraglutide, semaglutide, dulaglutide).
6]Costs are high,education on how to inject is required.
Acute pancreatitis may occur
Gastrointestinal side effects are common
Worsening of pre-existing retinopathy
7] recommends GLP-1 RAs as the first injectable instead of insulin in carefully selected patients:
- ASCVD (or very high risk of ASCVD)
- Chronic kidney disease and albuminuria
- need to minimise hypoglycaemia
- need to minimise weight gain or promote weight loss
47
People who have had diabetes for several years and who are taking medications, have markedly reduced____.
incretin responses
48
The lack of release of GLP-1 in response to food is a contributor to ____
hyperglycemia
49
Drug Information __GLP-1 Receptor Agonists (GLP-1 RAs)
semaglutide, dulaglutide and extended release exenatide
-given weekly
liraglutide, lixisenatide,
- given daily
shorter acting drugs more impact on post prandial glucose
These are all injectable apart from oral semaglutide
Oral semaglutide
- must be administered daily
- first thing in the morning on an empty stomach a small sip of water
- wait at least 30 minutes before taking any other medication,food or drink.
50
GLP-1 RAs—Dose Information
Exenatide
-5 micrograms twice daily—take at least six hours apart and within one hour of a main meal
-Allow one month and then double dose if needed
-10 micrograms, twice daily, maximum limit
Exenatide modified release
-2mg once weekly—no need to escalate the dose
Liraglutide
-0.6mg daily
-Allow at least one week and then increase to 1.2mg daily
-1.8mg daily maximum limit
Lixisenatide
-10 micrograms once daily—take within one hour of the first meal of the day or the evening meal
-Allow at least two weeks and then double the dose
-20 micrograms once daily maximum limit
Semaglutide
-Starting dose 0.25 mg weekly, increasing after 4 weeks to 0.5 mg weekly and after at least 4 weeks if required to maximum dose 1 mg weekly
Dulaglutide
-Starting dose is 0.75 mg weekly in monotherapy and can be considered in those who are frail for example those ≥ 75 years.
-For add on therapy use 1.5 mg weekly.
-If further glycemic control required, the dose can be increased to 3mg after at least 4 weeks and to 4.5mg after a further 4 weeks .
When starting GLP-1 RAs, no change is needed to doses of metformin, pioglitazone or SGLT2 inhibitors, but doses of sulfonylureas and insulins should be reduced initially and can be titrated if needed.
DPP4-I must be stopped when GLP-1 RA are started
51
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DPP-4 Inhibitors
Examples?
How long do effect last?
How do they work?
What are additional advantages?
Treatment Risks?
```
sitagliptin, vildagliptin, linagliptin, alogliptin, saxagliptin
have long half-lives
given once daily
85% inhibition 24 hours later,effectively restores circulating GLP-1 to the levels of a non-diabetic patient.
cleave the incretin hormones glucagon-like peptide-1 (GLP-1),glucose-dependent insulinotropic peptide (GIP),inactivating them
results in increased blood concentration of these incretins,augment the glucose-dependent insulin and glucagon responses,reducing blood sugar
DPP-4 inhibitors can preserve beta cell mass and function
neutral with ASVD
saxagliptin and possibly alogliptin increase the risk of hospitalisation for heart failure.
inhibiting other peptidases in this group, such as DPP-8 and 9 can cause renal and skin toxicity
Common side effects: gastrointestinal disturbances, nasopharyngitis. Pancreatitis is a rare but severe
DPP-4 inhibitors + sulphonylureas = increased risk of hypoglycaemia due to the sulfonylurea.
all drug are safe in renal disease except linagliptin are excreted renally. excreted in bile
52
DPP-4 Inhibitors—Dose Information
flat dose structure so the dose should not be increased.
Sitagliptin
-100mg once daily
Saxagliptin
-5mg once daily
Linagliptin
-5mg once daily
Vildagliptin
- 50mg twice daily (once in combination with a sulfonylurea)
- should not be used in hepatic impairment or if ALT or AST is > 3x normal.
Alogliptin
-25mg once daily
53
SGLT-2 Inhibitors
1]Examples?
2]How do they work?
3]What are additional advantages?
4]Drug Side Effects?
1]Sodium-glucose co-transporter-2 is a sodium dependent glucose transport protein.
dapagliflozin, canagliflozin, empagliflozin, ertugliflozin
2]cause less glucose to be reabsorbed from the urine, decreasing blood sugar levels
glucose-lowering mode of action requires normal glomerular-tubular function in the kidneys,the effect is reduced in renal impairment.
dapagliflozin and empagliflozin should not be initiated if the eGFR is less than 60 ml/min/1.73m2.
can continue until the eGFR is consistently < 45 ml/min/1.73m2 and then must be stopped.
lower doses of canagliflozin and empagliflozin should be used when the eGFR is between 45 and 60 ml/min/1.73m2.
renal protective effects in the CREDENCE trial, canagliflozin
For treatment of diabetic kidney disease
add on to ACE-inhibitors or ARBs
a dose of 100 mg canagliflozin once daily
3]action independent of the actions of insulin.
less risk of hypoglycemia
less over-stimulation of the pancreatic beta cells
causing weight loss
small reduction in blood pressure.
4] bladder: increased risk of urinary tract infection,vulvovaginitis in women,balanoposthitis in men --due to the increased amount of glucose in the urine encouraging fungal and bacterial growth.
Bone: increased risk of fracture with canagliflozin,
increased risk of amputation with the previous amputation seen with ertugliflozin
increased risk of diabetic ketoacidosis (DKA) without significant hyperglycemia
54
SGLT-2 Inhibitors– Dose Information
Dapagliflozin
- 10mg once daily—no increase is needed
- 10mg once daily maximum limit
Canagliflozin
- 100mg once daily—taken before breakfast
- Increase if initial dose is tolerated, additional glucose lowering is required and eGFR is >60ml/min/1.73m2
- 300mg once daily maximum limit
- 100mg can now be initiated down to an eGFR of 45 ml/min/1.73m2 and to an eGFR of 30 in those with high levels of albuminuria (ACR >300mg/g, approximately 30mg/mmol)
- Do not initiate if eGFR <30ml/min/1.73m2 but can be continued if already started until dialysis or transplantation.
Empagliflozin
- 10mg once daily
- Increase if initial dose is tolerated, additional glucose lowering is required and eGFR is >60ml/min/1.73m2
- 25mg once daily maximum limit
Ertugliflozin
- Starting dose 5mg once daily
- In patients tolerating this, the dose can be increased to 15 mg once daily if required
55
Case scenario
50-year-old,concerned about weight gain,need to urinate all the time,had a couple of urinary tract infections in the last six months,several episodes of fungal balanitis treated with clotrimazole cream
currently taking metformin 1g twice a day,never misses a dose
not had any cardiovascular complications and no retinopathy.
BMI: 33.2 kg/m2 (gain of 3kg in six months)
HbA1c: 7.9% (63 mmol/mol)
BP: 144/92 mmHg
eGFR: 64 mL/ minute/1.73 m2
his medication needs to be increased.
Which?
Dulaglutide 1.5mg weekly
After at least 4 weeks the dose can be increased to 3mg weekly and to 4.5mg weekly after an additional 4 weeks.
use of SGLT2i or GLP-1 where it is important to avoid further weight gain and aim to achieve weight loss.
recommend other non-insulin agents if metformin alone hasn’t worked, rather than going straight to insulin tends to increase body weight.
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Choosing Glucose-Lowering Drugs
Non-insulin Agents
```
taking into account:
-HbA1c level
-weight
-renal function
-comorbidities
patient’s acceptability of
-number of doses
-how close they have to be taken to a meal
-whether or not an injectable drug will be accepted
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57
Insulin and CSII
What are the main relative contraindications?
How can contraindications be managed?
no significant, absolute contraindications to using insulin
widely used in pregnancy and breastfeeding,with other co-morbidities
Continuous subcutaneous insulin infusion (CSII) is an alternative to multiple daily injections.
main relative contraindications would be concerns about weight gain in already obese patients and the risk of hypoglycemia.
managed by being cautious with dose increases and reducing the dose if hypoglycemic episodes occur
58
The 2021 ADA Standard recommendation for the pharmacologic therapy for Type 1 Diabetes is:
should be treated with multiple daily injections of prandial and basal insulin, or continuous subcutaneous insulin infusion.
should use rapid-acting insulin analogs to reduce hypoglycemia risk.
should receive education on how to match prandial insulin doses to carbohydrate intake, pre-meal blood glucose, and anticipated physical activity.
59
Under what circumstances is insulin considered as first injectable?
Consider insulin as first injectable if:
- HbA1c is very high >97mmol/mol (11%)
- Symptoms of catabolism are present – weight loss, polyuria, polydipsia suggesting insulin deficiency
- Type 1 diabetes is a possibility
- evidence of ongoing catabolism
- symptoms of hyperglycaemia
- A1C levels >10% [86mmol/mol] or blood glucose levels are very high (>=300mg/dL [16.7mmol/L])
60
Different Types of Insulin
Human insulin
- produced in a laboratory by growing insulin proteins.
- cheaper and recommended first line.
- short acting insulins take longer to work.
Human analogue insulins
- made in the same way
- difference being that amino acids have been modified to produce a specific characteristic.
- act faster,mealtime doses can be taken at the start of a meal.
- more expensive
Animal insulin
-pancreas of pig or a cow
Continuous subcutaneous insulin infusion (CSII)
-external pump is attached to the patient by a subcutaneous needle and delivers insulin continuously from a refillable storage reservoir.
Biosimilar insulins ‘follow on insulins’
-complex biological products
-not interchangeable at the point of dispensing
-slightly cheaper than the comparator insulin.
-
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Insulin Length of Action
Short Acting/Rapid
Short Acting/Rapid
- rapid onset and short duration of action
- mimic the endogenous insulin, deal with the glucose load after a meal
- used for basal plus and basal bolus regimens and in insulin pumps
- soluble insulins ( subcute)work within 30–60 minutes of injection and last for up to eight hours
- rapid-acting analogues act faster (within 15 minutes) and last for only 2–5 hours[ideally be injected immediately before meals]
- RA advantages over SA: improved glucose control, reduction of HbA1c, and reduction in the incidence of severe hypoglycaemia, including nocturnal hypoglycaemia.
- human short-acting insulins include Actrapid, Humulin S and Insuman Rapid
- apid-acting analogues include Humalog (u100 and 200), Insulin lispro Sanofi, NovoRapid, Apidra
- ultra fast-acting analogues available in the UK include Fiasp and Lyumjev, which have onset in a few minutes and a duration of 1–3 hours.
- rapid-acting insulin analogues (insulin aspart, insulin glulisine and insulin lispro).
- injected intravenously, soluble insulin has a short half-life of only a few minutes and its onset of action is instantaneous. [most appropriate form of insulin for use in diabetic emergencies]
- routine use of post-meal injections of rapid-acting insulin should be avoided associated with poorer glucose control, an increased risk of high postprandial-glucose concentration, and subsequent hypoglycaemia
62
Insulin Length of Action
Intermediate-acting
- slower and longer acting
- mimic the effect of basal insulin which is produced throughout the day
- onset is 30-90 minutes and duration 11–24 hours depending on the product.
- human insulins
- examples: Humulin I[isophane insulin], Insuman Basal and Insulatard.
63
Insulin Length of Action
long-acting
- analogue insulins with onset 30–60 minutes and duration 24 hours for insulin glargine products.
- examples: insulin glargine 100 units/ml (Abasaglar, Semglee (biosimilars), Lantus) and insulin glargine 300 units/ml (Toujeo).
- insulin detemir (Levemir) may require twice-daily dosing as its duration is shorter
- Toujeo may last up to 36 hours.
64
Insulin Length of Action
Very Long-Acting
- useful when external help is needed to administer insulin
- onset 30–90 minutes
- duration > 42 hours
- example: insulin degludec.
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Insulin Facts
biosimilar insulins
- 200 units/ml, 300 units/ml and 500 units/ml insulins
- different pen and multiple different delivery devices
- all insulin should be prescribed by brand
- to avoid receiving the wrong insulin and potentially fatal dosing errors.
66
Mixed or Biphasic Insulin
1]How does the combination work?
2]What time profiles can be expected?
-pre-mixed and contain a measured combination of short and intermediate-acting insulin.
1]short acting insulin acts on the glucose taken in at a meal and the intermediate acting insulin continues to control blood sugar after the effect of the short-acting insulin has worn off.
2]available in different combinations of short and intermediate insulin
give different time profiles of action in terms of onset and duration: 30:70, 25:75 or 50:50 ratios of short to long-acting insulin available in mixed insulins.
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Insulin
- polypeptide hormone secreted by pancreatic beta-cells
- increases glucose uptake by adipose tissue and muscles,
- suppresses hepatic glucose release ( gluconeogenesis)
- role of insulin is to lower blood-glucose concentrations in order to prevent hyperglycaemia and its associated microvascular, macrovascular and metabolic complications.
- natural profile of insulin secretion: basal insulin (a low and steady secretion of background insulin that controls the glucose continuously released from the liver) and meal-time bolus insulin (secreted in response to glucose absorbed from food and drink).
- true insulin allergy is rare
- Human insulin and insulin analogues are less immunogenic than animal insulins.
- Insulin is inactivated by gastro-intestinal enzymes and must therefore be given by injection
- subcutaneous route is ideal
- injected into a body area with plenty of subcutaneous fat: abdomen (fastest absorption rate), outer thighs/buttocks (slower absorption compared with the abdomen or inner thighs).
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factors affecting the rate of absorption of insulin is?
Local tissue reactions,
changes in insulin sensitivity,
injection site, (abdomen, thigh, buttocks)
blood flow,
depth of injection,(inject 90degree lift skin fold in >6mm needle)
needle length (4,5,6 mm) and
the amount of insulin injected
Increased blood flow around the injection site due to exercise - increase insulin absorption.
69
repeatedly injecting into the same small area cause?
- Lipohypertrophy( fatty, rubbery tissue) due to poor injection technique
- erratic absorption of insulin,
- contribute to poor glycaemic control
- minimised by using different injection sites in rotation
- advised not to use affected areas for further injection until the skin has recovered
- Injection sites should be checked for signs of infection, swelling, bruising, and lipohypertrophy before administration
70
ADA recommendation of Initiating Insulin
- starting with basal insulin at a dose of 10U/day or 0.1–0.2 U/kg/day.
- Options: [ modern analogue insulin (Abasaglar (insulin glargine U100), or isophane insulin (Insulatard or Humulin I.]
- choosing a fasting glucose target then titrate
- post-prandial readings- need for addition of prandial or mixed insulin.
-overbasalization: basal dose more than 0.5 IU/kg, high bedtime-morning or post-preprandial glucose differential, hypoglycemia (aware or unaware), and high variability.
- If no effect, the dose of insulin can be adjusted by 10–15% (or 2–4 U) once or twice weekly depending on fasting blood sugar readings
- continued until the fasting blood sugar target is reached, or the dose exceeds 0.5 U/kg/day.
outcome
-Once the fasting sugar target is reached (or the maximum dose is being taken HbA1c should be checked (after at least two months) review result
-If the HbA1c is not controlled then add GLP-1 agonist or another dose of insulin before meals particularly if the post-prandial glucose is too high
-with an injection of rapid-acting insulin before the largest meal (Basal plus)
by changing to biphasic insulin twice daily
71
Hypoglycemia Symptoms
- sweating
- pallor
- irritability
- hunger
- lack of coordination
- sleepiness
mild hypoglycemic episode: 15-20g of sugar 5 to 10 min not better then repeat
72
Hypoglycaemia Risk
- long-acting human insulin analogue once a day has a lower risk of hypoglycaemia than using human isophane insulin
- human insulin analogues[modified pharmacodynamics] give a more stable concentration of insulin throughout the day and reduce the risk of hypoglycaemia
73
NICE Guidelines for the first line use of long-acting human insulin analogues
if the patient:
- needs assistance to inject insulin,reduce the frequency of injections from twice daily to once daily
- lifestyle that is restricted by recurrent symptomatic hypoglycaemic episodes
otherwise
- twice-daily isophane insulin injections+ oral glucose-lowering drugs
- cannot use the device to inject human isophane insulin
74
Education Program for patient on Insulin
Who should manage the patient?
How should the education program be conducted?
What could the education program involve?
-a multidisciplinary team[ doctor,diabetic specialist nurse or a practice nurse with experience, specialist pharmacist, psychologist.]
- Group classes cost less than individual teaching
- benefit from the group atmosphere and meeting others with the same issue
- injection technique
- telephone support
- self-monitoring
- dose titration
- diet review
- driving guidance
- hypoglycemia or rapid changes in blood sugar management
75
Insulin Delivery Device - Factors
The choice of insulin
-locally available
Patient factors
-manual dexterity and any visual impairment
Type of device
Other equipment requirements
-blood sugar (a monitoring machine, lancets and test strips)
76
Six steps to Insulin safety
THE RIGHT PERSON
-consider peference, lifestyle,capacity,know your own insulin and risk
THE RIGHT INSULIN
- 100 units/ml (U100)[ means concentration not dose] most common use
-color coding ( orange- URA, light blue- RA, pink-SA, Dark Blue-IA, Green- LA)
THE RIGHT DOSE
-use units not IU
THE RIGHT DEVICE
-syringes, catridegs for pens, prefilled pens, infusion set, pumps
THE RIGHT WAY
-insulin suspension, absorption rate, liphypertrophy, disposal of sharps, site selection, site rotation, insulin storage ( @ room temperature, avoid sunlight)
THE RIGHT TIME
77
Adding rapid-acting insulin before the largest meal
- start with a dose of 4 U or 0.1 U/kg or 10% of the basal dose
- adjust by 10–15% (or 1–2 U) once or twice a week until blood sugar targets are reached
- if fasting glucose low, consider lowering basal dose by 4 units per day or 10% of basal dose.
78
Changing to biphasic insulin twice daily
- decide how to divide the current basal dose, for example 2/3 in the morning and 1/3 in the evening, or half and half—looking at the pattern of self-monitoring results may help with this
- adjust the dose by 1–2 U or 10–15% once or twice weekly until blood sugar targets are reached
79
Basal Bolus Regimen
What is the basal bolus regimen?
How are the rapid injections administered and the dose adjusted?
How much insulin is given as a basal dose and how much as a bolus?
- Basal insulin is combined with two or more injections of rapid acting insulin before meals.
- rapid injections should be started at the same dose as previously mentioned and adjustments done by 1–2 U or 10–15% once or twice a week until the blood sugar targets are reached.
- approximately half the insulin is given long-acting once a day and half is given as boluses before meals.
80
Insulin
```
1] Rapid Acting
- Insulin Lispro (Humanlog)
-Insulin Aspart ( Novolog)
-Insulin Glulisine ( Apidra)
2] Short Acting
- Regular Insulin ( Humulin R)
3] Intermediate Acting
-Isophane NPH( Humulin N)
4]Long Acting
- Detemir( levemir)
- Glargine ( Lantus)
```
81
Metformin [Biguanides]
```
Indication
- T2DM
-PCOS
MOA
- Decrease Gluconeogenesis
-Increase peripheral Insulin Sensitivity
A/E
-Lactic Acidosis
-GI distress
-Weight loss
-B12 Deficiency
Contraindication
-GFR< 30ml/min
```
82
Sulfonylureas
suffix [ -ide]
```
Chlorpropamide, Tolbutamide[1st G]
MOA
-Stimulate release of Insulin
Indication
-T2DM
A/E
-Hypoglycemia
-CVS toxicity
Consideration
-Beta-blocker reduce effect
-avoid during pregnancy and breast feeding
-avoid alcohol
```
```
Glyburide, Glipizide [2nd G]
MOA
- block K+ channel in beta cell
-Stimulate release of Insulin
Indication
-T2DM
A/E
-Hypoglycemia
Consideration
-more potent
-Beta-blocker reduce effect
- avoid breast feeding
-avoid alcohol
```
83
Thiazolidinediones
suffix [ -glitazones]
```
Pioglitazones, Rosiglitazones, Troglitazones
MOA
- bind PPAR-gamma
-decrease insulin resistance
Indication
-T2DM
A/E
-weight gain
-heart failure
-myalgia
-hypoglycemia
-URTI
Consideration
- increase risk bladder CA
-increase risk Fracture
-monitor liver enzymes
```
84
Alpha glucosidase inihibitor
Acarbose [precose]
Miglitol [ Glyset]
```
MOA
-AGI
-delay absorption of carbo
Indication
-T2DM
A/E
- Flatulence
-Diarrhea
-Cramps
-Anemia
Consideration
-monitor LFT
-Oral glucose for hypoglycemia
```
85
Meglitinides
suffix [ -glinide]
Repaglinides, Nateglinide
```
MOA
-increase insulin release
Indication
-T2DM
A/E
- Hypoglycemia
Consideration
-Eat within 30 mins
-Gemfibrozil ( anti-cholesterol, fibrate) increase risk of Hypoglycemia
-short half-life
```
86
DPP4-i
(peptide)
suffix [-gliptin]
```
Sitagliptin [ januvia]
Saxagliptin [ onglyza]
MOA
-increase insulin release
Indication
-T2DM
A/E
-pancreaitis
-URTI
-Inflammation
-Steven-Johnson Syndrome
Consideration
- Add-on agent
```
87
Amylin
--mlin--
```
Pramlintide(Symlin)
MOA
-synthetic amylin analog
Indication
-T2DM
-supplement mealtime insulin
A/E
-Nausea
-Skin reaction at inj site
Consideration
-Hypoglycemia if combined with insulin
-delay absorption of oral drugs
```
88
GLP1-RA
suffix [ -tide]
Exenatide,exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide
```
MOA
-Incretin Memetics
Indication
-T2DM
A/E
-Hypoglycemia
-N & V
- Diarrhea
- Ca Thyroid
-Pancreatitis
-Renal Failure
Consideration
-Exenaide 1 hour after other meds
-Adjunt Therapy
```
89
Glucogon
```
Glucagen
MOA
- increase glucose
Indication
-Hypoglycemia Emergency
A/E
- N & V
Consideration
- reconsitue powder
-consume oral carbo
- 50% Dextrose IV if no effect
```
90
If insuling injection is painful
- use shorter needle
| - numb the area before injecting
91
Insulin Injection Problem
Painful injections
- review injection technique[accidentally injecting intramuscularly]
- needles are not being re-used
- insulin is not being given straight from the refrigerator
- shorter needle
- numb the area with ice for 15–20 seconds before giving the injection
Bleeding and bruising
- reassure that a small bleed may happen, resolves spontaneously
- gentle pressure for 1–2 minutes after the injection to minimize bruising
- not to rub the area
Redness, swelling or itching at the injection site
- local reactions usually resolve over days
- persists for longer than 2–4 weeks, consider switching insulin[analogue from]
- exclude allergy to soap or cosmetics
- trying a different preparation in the same class
Lipohypertrophy (accumulation of lumps of fat under the skin)
- rotating injection sites
- rotating more widely will mean no further occurrence
- may take weeks to recover
Leakage of insulin
- withdrawing the needle sooner than the 10–15 seconds
- necessary to leave the needle in for longer if large doses
- a second dose should not be injected to compensate for leaked insulin but close monitoring of blood sugar
92
Continuous subcutaneous insulin infusion (CSII)
1. How does the pump work?
2. How do you program the pump?
- alternative to multiple daily injections
- use for more than 35 years
- patients with type 1 diabetes use an insulin pump.
1.external pump is attached to the patient by a subcutaneous needle
delivers rapid acting insulin continuously from a refillable storage reservoir
2.can be programmed in various different ways
usually a basal rate throughout the day with boluses to cover meals triggered by the user
93
multiple daily injections [MDI]
CSII is generally more expensive
94
ideal candidate for CSII
regular hypoglycemic attacks.
95
Hybrid Devices
can both monitor glucose and administer insulin
96
when to consider CSII and CGM.
1. Who should consider pump therapy?
2. What are the benefits of CSII?
1.
- already using CSII successfully
- Adults, children and adolescents with T1DM who require intensive insulin therapy by MDI or CSII
- all children and adolescents < 7 years of age.
2.
- improve glycemic control
- reduce severe hypoglycaemia
- improve quality of life and patient satisfaction
- useful in those with frequent hypoglycaemia or hypoglycaemia unawareness
97
Advantages and Disadvantages of changing from MDI to CSII therapy?
```
Advantages
Flexibility
-no need to inject regularly
Control of HbA1c
-less insulin was used
-achieved ADA targets
-less episode of hypoglycemia per week
Prevention of complications
-initial tight glycemic control reduce risk of retinopathy
Accuracy of insulin delivery
-an deliver a dose as small as 0.1 U
-little risk of human error
-temporary basal rates can be calculated
basal rate increase after comsumption of high glycemic food or reduce if strenous exe is done
Avoidance of the dawn phenomenon
-dawn phenomenon is an early morning increase in blood sugar level
-due to night-time spikes in production of hormones such as cortisol and glucagon
-CSII can reduce this effect
```
```
Disadvantages
Side-effects
-infections at the needle site
Risk of diabetic ketoacidosis (DKA)
-pump malfunctions, patient isn’t aware
-always carry a back-up supply of insulin
Loss of confidentiality
-machine may draw attention
Monitoring
-more frequent blood sugar monitoring may be needed
Cost
-high
```
98
how to manage a pump failure
| what we need to prescribe for the patient’s emergency kit.
carbohydrate counting
knowledge of ideal pre/post meal values
how to adjust insulin to take into account vigorous exercise
what to do when unwell
99
criteria for the use of CSII in patients
- must be C-peptide deficient and have an HbA1c that is not controlled with MDI insulin therapy
- significant dawn phenomenon
- erratic lifestyle e.g. due to shift work, making it difficult to control blood sugar with MDI therapy
- severe insulin resistance
100
C-peptide?
- released by the beta cells of the pancreas when insulin is cleaved from proinsulin
- presence in the blood indicates the release of insulin
- If C-peptide is normal= insulin-resistant
101
T1DM, taking basal-bolus, acceptal sugar level throught the day, but HbA1C increasing, how to manage ?
- do occasional night time readings and test more often during the day
- trial for continuous glucose monitoring (CGM) CGM a 24-hour picture
- to identify episodes of hyperglycemia.
102
Continuous Glucose Monitoring (CGM)
a system whereby subcutaneous sensors measure the levels of glucose in the interstitial fluid
a proxy for blood sugar levels
103
CGM Types
There are two types of CGM.
Personal CGM machines
- used in real time to adjust food intake or insulin doses
Glucose Flash Monitoring
- affordable sensor, does not need calibration, and is read by sweeping a reader over the sensor on the upper arm
- measure current glucose,3-hour graph and current trend arrow
- downloaded onto software to assess 24 hour control.
CGM is expensive
104
The Guidelines to target CGM
NICE
- recommended forT1DM who have disabling hypoglycemia despite the use of optimal insulin therapy
- Targets for reduction in hypoglycemic episodes should be set
SIGN and ADA
- targeted at those with troublesome hypoglycaemia, particularly at night.
American Association of Clinical Endocrinologists
- for those with type 1 DM
- hypoglycemic unawareness or frequent hypoglycemia
- HbA1c over target
- hypoglycemia judged to be excessive, potentially disabling, or life- threatening
- requiring HbA1c lowering without increased hypoglycemia
- uring preconception and pregnancy
- all pregnant women with type 1 diabetes
- children and adolescents
105
What does bariatric surgery involve?
Bariatric or metabolic surgery refers to a variety of surgical procedures with a growing evidence base for producing weight loss, and in some cases, remission of diabetes.
106
Weight-loss Drugs
- metformin, SGLT2 inhibitors and GLP-1 receptor agonists
- cannabinoid receptor antagonists (no longer available)
- selective serotonin receptor agonist (no longer available)
- drugs which interfere with fat absorption
- drugs which speed up the metabolism or reduce appetite by increasing levels of norepinephrine or other neurotransmitters
107
Weight-loss Drugs
```
Orlistat
-lipase inhibitor
-reduces the absorption of dietary fat.
A/E
-flatulence and fecal incontinence due to increased amount of fat in the stool.
```
Sibutramine
-available since 1988
- inhibiting uptake of norepinephrine, serotonin and dopamine
A/E
- increased cardiovascular risk and was withdrawn in 2010
-increase HR and BP
Phentermine
- available since 1959
- stimulating the release of norepinephrine, serotonin and dopamine.
- structure similar to amphetamines
- 3.75 mg─15 mg combined with topiramate 23─92mg (Qysimia) potent weight loss drug
Bupropion
- anti-depressan
- used for smoking cessation
naltrexone
- reverse the effects of opiates
- decrease hunger and food cravings
- contraindicated in seizures or uncontrolled BP
- increase suicidal ideation
- need careful monitoring
Combo of B+N
- activate the melanocortin neurons in the hypothalamus
- resulting in a loss of appetite
- available since 2014.
Lorcaserin
-serotonin receptor (5-HT2C) agonist
-selective activation of serotonin receptors
-withdrawn to cancer concerns.
-avoid the valvulopathy seen with non-selective agonists such as fenfluramine
A/E
-headache, nausea, dizziness and fatigue.
-risk of serotonin syndrome if combo with other serotonin drug
-Monitor for depression and suicidal risk.
-Avoid in hepatic and renal failure.
Liraglutide
-higher dose specifically for weight loss.
-3 mg strength (1.2─1.8 mg for diabetes treatment)
-more expensive than orlistat
-injectable medication
-recommended BMI ≥ 30, or BMI ≥ 27 and ≥ 1 weight-related comorbidity
-Discontinue at 12 weeks if 5% weight loss is not achieved
A/E
-GI problem N&V
-avoid in IBD gastroparesis and previous pancreatitis
-increased risk of thyroid C-cell tumours.
Alternative treatments[no licen]
- herbal remedies
- prescribed by slimming clinics
- sold over the internet
- levothyroxine,
- laxatives,
- human chorionic gonadotrophin and -diuretics.
108
Bariatric Surgery
1.How many different types of bariatric surgery can you list?
2/Which of them cause post-operative nutrient deficiencies and which work the best?
3. long-term outcomes after bariatric surgery?
4. Complications?
- action is partly due to the physical effect of reducing the size of the stomach
- partly due to resulting hormonal changes
```
1.
1] Adjustable gastric band
2]Roux-en-Y Gastric Bypass
3]Vertical Sleeve Gastrectomy
4]Biliopancreatic DIversion with Duodenal Switch
5]Endobarrier
```
2.
-Biliopancreatic DIversion with Duodenal Switch cause nutritional deficiencies.
3.
- greater chance of going into dibetic remission 22 times more likely than medical Mx
- slightly less for sleeve gastrectomy
- significantly less for gastric banding
- reduce CV risk, DM microvascular complication
- able to stop some or all medication
- cost-effective at a BMI of over 35 kg/m2
4.
- vitamin and mineral deficiency
- osteoporosis
- operator-dependent
- reduced drug absorption
- Dumping syndrome
109
Adjustable gastric band
What are the likely advantages and disadvantages of the adjustable gastric band surgery?
-simplest method
- A small band is placed around the top of the stomach
- creating a pouch smaller than the original stomach.
- A balloon is attached to the band and can be inflated or deflated
- mimic feelings of fullness with less food
- access port under the skin.
- cause a reduction in calorie intake.
Adv
- done laparoscopically
- reversible.
DAdv
-weight loss and remission of diabetes is less likely
C/I
- make the patient unable or unwilling to comply with dietary restrictions
- severe mental health disease or history of substance misuse
- co-morbidities that make them unfit for surgery
- active gastrointestinal tract disease
- inflammatory bowel disease, gastric ulcers or severe esophagitis
110
Roux-en-Y Gastric Bypass
- open procedure or laparoscopically.
- commonest performed
- small stomach pouch is constructed separated from the main part
- A cut is then made across a part of the small intestine and that portion is brought up and attached directly to the stomach pouch.
- main part continues to make acid and enzymes needed for digestion
- smaller stomach needs to be reattached to the main GI tract with a “Y” configuration,
Deficiencies, most to least common
- Iron ( IDF) [ eat less meat, less HCL, thus less conversion of Fe3+ to Fe2+, the more absorbable form]
- Vitamin D (osteoporosis, osteopenia)[ reduce storage in adipose tissue- hypocalcemia]
- Vitamin B12/ folate deficiency[ reduce parietal cell- less intrinsic factor- pernicious anaemia]
- Vitamin A, D, E, K ( fat-soluble) [rare here, but common in Biliopancreatic Diversion
- A (night blindness), K ( alter clotting factor)
- ZInc [common in Biliopancreatic Diversion] [ reduce absorption in small intestine]
- deficient in macro-nutrients, particularly protein
- Protein restriction after surgery
- Hypoalbuminemia
111
Vertical Sleeve Gastrectomy
- a large part of the stomach is removed
- 10% reduce the size
- no re-routing
- food pass through the duodenal normally
112
Biliopancreatic Diversion with a Duodenal Switch
- sleeve gastrectomy+ distal end of the stomach connected directly to a portion of the small intestine(R-en-Y
- no pouch
- food bypasses a large part of the small intestine
- nutritional deficiencies.
- causes more weight loss than other forms
- bigger operation
113
Endobarrier
- inserted endoscopically
| - temporary barrier between the gut wall and food passing through the first part of the small intestine
114
Hormones that Regulate Satiety and Appetite
- GLP-1
- Peptide YY
- Leptin
- Ghrelin
115
GLP-1
| The mechanism for Weight Loss
- incretin hormone enhances insulin production in response to a meal
- increase in levels of GLP-1 after gastric bypass surgery
116
Peptide YY
| The mechanism for Weight Loss
- secreted by the L cells of the lower intestine in response to ingestion of food
- smaller amount produced in the oesophagus, stomach, duodenum and jejunum.
- increases absorption of water and electrolytes and inhibits gastric mobility
- decreases food intake
- effect on lipid metabolism and energy use
- increased after gastric bypass.
117
Leptin
| The mechanism for Weight Loss
- derived from adipose tissue
- key role in the control of food intake and body fat stores.
- significant resistance to leptin builds up= obesity
- Obese people have high levels of leptin but resistant
- stay the same or are lower after gastric bypass surgery
- markedly reduced after gastric stimulation.
118
Ghrelin
| The mechanism for Weight Loss
- first hormone identified to be related to hunger
- produced by the oxyntic glands in the stomach and intestine
- enhance feeding and weight gain
- pre-prandial rise in ghrelin levels in human
- significantly decreased after gastric stimulation and after gastric bypass
119
Nutrient Deficiencies
- obese people have nutritional deficiencies even before surgery
- after surgery, deficiency can affect eye sight
120
Given that their calorie intake is generally high, can you think of any mechanisms that underlie a general deficiency, or deficiency of any particular nutrients?
- over-consumption of processed foods
- relative lack of fruit, vegetables and other nutrient dense foods
- fat-soluble vitamins such as vitamin D can become sequestered in excess adipose tissue
- not be available for use by the body
- increase in vitamin D with the weight loss after surgery
- decreased physical activity outside reduce sun exposure and vit D production
- adipose tissue can function as an active endocrine organ
- increases the production of inflammatory cytokines
- chronic state of low-grade inflammation
- disturb nutrient absorption
121
post-operative Nutrient Deficiencies
mechanisms:
- decreased intake of food
- vomiting
- reduction of gastric secretions
- bypass of absorption surface areas
- deficiencies is proportional to the length of intestine bypassed
122
Drug Absorption after surgery?
- oral contraception is unreliable, avoid
- Pregnancy should be avoided during intensive weight loss in the 12-18 months following bariatric surgery.
- Non-oral contraceptives are safe and effective
- such as intrauterine devices, implants or condoms
- switch at least 4 weeks prior to surgery
- no difference in absorption of digoxin and paracetamol
- increased absorption of penicillin
- increase in absorption of atorvastatin
123
Medication Doses after surgery?
- closely monitor drugs with a narrow therapeutic window, using blood levels if necessary
- closely clinically monitor the effects of other drugs, particularly those used to treat psychiatric conditions
- avoid NSAIDs due to the risk of ulceration
- avoid slow-release drugs in favour of immediate release ones
- avoid effervescent and enteric-coated preparations
- avoid very large tablets (greater than 10mm diameter) that cannot be crushed
- closely monitor diabetes and hypertension as doses of medications needed for these conditions may drop with rapid weight loss
124
Do you know the criteria for referral for bariatric surgery?
- above BMI >40
| - at a lower BMI with co-morbidities such as diabetes or cardiovascular disease.
125
Initial tests before referring for bariatric surgery?
initial blood tests
abdominal ultrasound if there is a suggestion of biliary disease
imaging to look for hernias (endoscopy or barium meal)
126
9 mth post-op,half an hour after eating she feels very sick and bloated with palpitations, sweating and diarrhea. Two to three hours later she feels faint, weak and confused and notices that her blood sugar has dropped. The symptoms then resolve, recurring again next time she eats.
Dx?
Dumping syndrome
- complication of bariatric surgery
- more commonly seen in those who do not follow their post-operative diet carefully
- occurs due to rapid gastric emptying
two forms:
1]early dumping syndrome (10-30 minutes after a meal)
-caused by the rapid movement of fluid into the intestine
-three times as common
-nausea, abdominal pain, diarrhoea,bloating,
2]late dumping syndrome (2-3 hours after a meal)
- caused by rapid movement of sugar into the intestine
- release insulin- hypoglycemia
- hypoglycemia,
patient can experience both
CF of Both:
- sweating
- weakness
- dizziness
- flushing
- palpitations
127
Sigstad’s Scoring System
a score <4 suggests other diagnoses
a score of >7 suggests dumping syndrome.
- Shock
- Fainting, syncope, unconsciousness
- Desire to lie or sit down
- Breathlessness, dyspnea
- Weakness, exhaustion
- Sleepiness, drowsiness, apathy, falling asleep
- Palpitation
- Restlessness
- Dizziness
- Headaches
- Feeling of warmth, sweating, pallor, clammy skin
- Nausea
- Abdominal fullness, meteorism
- Borborygmus
- Eructation
- Vomiting
128
Further Tests for Dumping Syndrome?
MGTT
- fasts for 8 hours, test for glucose and hematocrit , pulse and blood pressure every 30 mins interval
- if at 30 minutes the hematocrit has gone up by more than three per cent or the pulse rate has gone up by more than 10 beats per minute = Dx
- hypoglycemia between 120 and 180 minutes =Dx
Gastric Emptying Scintigraphy test
- a meal containing a small amount of radioactive material
- abdomen is scanned
- rate of gastric emptying measured at 1, 2, 3 and 4 hours after the meal
129
Treatment for Dumping Syndrome?
| What dietary changes should Marianna make?
- Not drink any liquid until at least 30 minutes after a meal
- Eat five or six small meals per day instead of three larger ones
- Increase their intake of complex carbohydrates, protein and fibre
- Increase the thickness of their food, for example by adding guar gum or pectin
- Avoid sugar and sugary food or drink
- Try lying down for 30 minutes after a meal as that can help to reduce symptoms.
If this doesn’t work
- octreotide acetate injection
- short-acting,sub-cutaneously 2-4 times a day
- the long-acting version is given intra-muscularly 1/4weeks.
- inhibits the release of insulin and slows gastric emptying
If this doesn’t work
-referred back to their bariatric surgeon
130
Islet Cell Transplant Therapy
- Allogenic pancreatic islet cell transplantation for T1DM
- used particularly for those with hypoglycemia unawareness
- beta cell from brain dead donor- purified in lab- inject into patient's portal vein under GA
- risk of rejection, immunosuppressant for life
Adv
- Severe hypoglycemia was reduced
- insulin independent
- needed less than half of their original dose
131
Diagnostic Criteria for Diabetes in Children and Adolescents
- fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) or -2–h plasma glucose (PG) ≥ 200 mg/dL (11.1 mmol/L)
- the use of diagnosis through raised HbA1c is not recommended in this age group.
- the emergency diagnosis of diabetes in children can be difficult as a child may be acutely ill with abdominal pain, vomiting, and drowsiness without necessarily having preceding weight loss and thirst.
The ADA presents the following diagnostic criteria:
-FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.
OR
2 h PG ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L).
Always assume that diabetes in children is Type 1 even if overweight
medical emergency
suspicion of diabetes and elevated glucose, ketones are present or not refer to pediatric team
132
Risk factor for Diabetes in Children and Adolescents
- obesity
- parents or grandparents with diabetes
- ethnicity
- socio economic status
- urban or rural dweller
- level of activity
133
Treatment Goals for Diabetes in Children and Adolescents
| ADA and NICE recommendation
ADA
- HbA1c A target of <7% (53mmol/mol) for both T1 & T2DM
- <7.5% (58mmol/mol) for T1DM cannot articulate hypoglycaemic symptoms/hypoglycaemia unawareness/
- <6.5% (48mmol/mol) for T2DM w/o significant hypoglycaemia
NICE
- 6.5% (48 mmol/mol) for children both T1 &T2
134
Blood Sugar Targets
| For children
Blood glucose goal range for T1DM [ADA]
1. Before meals
- 90-130 mg/dL
(5. 0-7.2 mmol/L)
2. Bedtime/overnight
- 90-150 mg/dL
(5. 0-8.3 mmol/L)
3.A1C
-<7%
(53 mmol/mol)
4. Rationale
- A lower goal range (<6.5% [48 mmol/mol])
- without excessive hypoglycemia
Blood glucose goal range for T1DM [NICE]
1.On waking or before meals
-Plasma glucose of
72–126 mg/dL (4–7 mmol/L)
2.After meals
-Plasma glucose of
90–162 mg/dL (5–9 mmol/L)
3.When driving (for adolescents who drive)
-Plasma glucose of
≥90 mg/dL (5 mmol/L)
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Insulin For children
-basal-bolus regime from the outset+continuous subcutaneous insulin infusion/MDI
glucose monitoring
-Finger prick testing not popular with children
-continuous monitoring and sensors inserted
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Complications of Diabetes For children
-Cardiovascular events rare
-may have sub-clinical cardiovascular abnormalities within ten years of diagnosis with type 1 diabetes
-
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management of cardiovascular risk factors and prevention in children
T1DM
1. BP
- check BP at every review and confirm on three separate days if BP is high
- treat with 3–6 months of lifestyle modification
- treat initially with ACEi or ARB
- aim for a BP of less than the 90th percentile for age, sex and height
2. lipids
- fasting lipids age>10,2 or over if significant family history of CVD, repeat after 3─5 years
- statins after a trial of lifestyle
- if the LDL cholesterol is over 160 mg/dL (4.1 mmol/L), or over 130 mg/dL (3.4 mmol/L)
- aim for an LDL of <100 mg/dL (2.6 mmol/L)
- statins teratogenic discuss contraception with adolescent girls
3. Smoking
- a smoking history at every appointment
- including passive smoking
- discourage smoking, e-cigarette use, smoking cessation therapy
4. nephropathy
- albumin: creatinine ratio (ACR) in the urine every year start at 10 years old
- eGFR at diagnosis
- starting an ACEi or ARB if the ACR is more than 30 mg/g (3.5 mg/mmol) in at least two out of three urine samples
5. retinopathy
- first eye examination at the age of 10
- repeat annually
6. neuropathy
- comprehensive foot examination at the age of 10
T2DM
1. BP
- at each review
2. lipids
- Measure once control is achieved and annually
3. Smoking
- same
4. nephropathy
- eGFR and ACR at diagnosis and annually
5. retinopathy
- screening at diagnosis and annually
6. neuropathy
- screening at diagnosis and annually
7. non-alcoholic fatty liver disease (NAFLD)
- LFTs at diagnosis and annually
8. obstructive sleep apnoea (OSA)
- Ask about symptoms at each visit.
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Disordered Eating Behavior
Diabulimia
- adolescents with T1DM reduce insulin doses to lose weight
- 40 percent of women, ages of 15–30
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signs of diabulimia
- HbA1c 9.0% (75 mmol/mol) or higher on a continuous basis
- unexplained weight loss
- persistent thirst/frequent urination
- preoccupation with body image
- blood sugar records o not match HbA1c results
- depression, mood swings and/or fatigue
- secrecy about blood sugars, shots and or eating
- repeated bladder and yeast infections
- low sodium/potassium
- increased appetite especially in sugary foods
- cancelled doctors' appointments
