Read all about Diabetes melitus in 30mins
Definition
Diabetes mellitus
(DM) is a disease of inadequate control of blood levels of glucose
Diabetes
mellitus is a
condition defined by persistently high levels of sugar (glucose) in the blood
Diabetes is a
chronic disease that occurs either when the pancreas does not produce
enough insulin or when the body cannot effectively use
the insulin it produces. Insulin is a hormone that
regulates blood sugar. Hyperglycaemia, or raised blood sugar, is a common
effect of uncontrolled diabetes and over time leads to serious damage to many
of the body's systems, especially the nerves and blood vessels
a disease in
which the body’s ability to produce or respond to the hormone insulin is
impaired, resulting in abnormal metabolism of carbohydrates and elevated levels
of glucose in the blood.
a
variable disorder of carbohydrate metabolism caused by a combination of
hereditary and environmental factors and usually characterized by inadequate
secretion or utilization of insulin, by excessive urine production, by
excessive amounts of sugar in the blood and urine, and by thirst, hunger, and
loss of weight
6 key facts about diabetes
- The number of people with diabetes
rose from 108 million in 1980 to 422 million in 2014. Prevalence has been
rising more rapidly in low- and middle-income countries than in
high-income countries.
- Diabetes is a major cause of
blindness, kidney failure, heart attacks, stroke and lower limb
amputation.
- Between 2000 and 2016, there was a
5% increase in premature mortality from diabetes.
- In 2019, an estimated 1.5 million
deaths were directly caused by diabetes. Another 2.2 million deaths were
attributable to high blood glucose in 2012.
- A healthy diet, regular physical
activity, maintaining a normal body weight and avoiding tobacco use are
ways to prevent or delay the onset of type 2 diabetes.
- Diabetes can be treated and its
consequences avoided or delayed with diet, physical activity, medication
and regular screening and treatment for complications.
TYPES OF DIABETES
Type 1 diabetes:
Type 2 diabetes: The body either doesn’t make enough insulin or the
body’s cells don’t respond normally to the insulin. This is the most common
type of diabetes. Up to 95% of people with diabetes have Type 2. It usually
occurs in middle-aged and older people. Other common names for Type 2 include
adult-onset diabetes and insulin-resistant diabetes.
This type of diabetes is largely the result of
excess body weight and physical inactivity.
Symptoms may be
similar to those of type 1 diabetes, but are often less marked. As a result,
the disease may be diagnosed several years after onset, after complications
have already arisen.
Until recently,
this type of diabetes was seen only in adults but it is now also occurring
increasingly frequently in children.
Prediabetes: This type is the stage before Type 2
diabetes. The blood glucose levels are higher than normal but not high enough
to be officially diagnosed with Type 2 diabetes.
Gestational diabetes:
Less
common types of diabetes include:
Monogenic diabetes syndromes: These are rare inherited
forms of diabetes accounting for up to 4% of all cases. Examples are neonatal
diabetes and maturity-onset diabetes of the young.
Cystic fibrosis-related diabetes: This is a form of
diabetes specific to people with this disease.
Drug or chemical-induced diabetes: Examples of this
type happen after organ transplant, following HIV/AIDS treatment or are
associated with glucocorticoid steroid use.
HEALTH IMPACT
Over
time, diabetes can damage the heart, blood vessels, eyes, kidneys, and nerves.
- Adults with diabetes have a two- to three-fold increased risk
of heart attacks and strokes.
- Combined with reduced blood flow, neuropathy (nerve damage)
in the feet increases the chance of foot ulcers, infection and eventual
need for limb amputation.
- Diabetic retinopathy is an important cause of blindness, and
occurs as a result of long-term accumulated damage to the small blood
vessels in the retina. Diabetes is the cause of 2.6% of global blindness.
- Diabetes is among the leading causes of kidney failure.
THE RISK FACTORS OF DIABETES
Risk
factors for Type 1 diabetes include:
- Having a
family history (parent or sibling) of Type 1 diabetes.
- Injury to
the pancreas (such as by infection, tumor, surgery or accident).
- Presence of
autoantibodies (antibodies that mistakenly attack your own body’s tissues
or organs).
- Physical
stress (such as surgery or illness).
- Exposure to
illnesses caused by viruses.
Risk factors for Prediabetes and Type 2 diabetes include:
- Family
history (parent or sibling) of Prediabetes or Type 2 diabetes.
- Being
African-American, Hispanic, Native American, Asian-American race or
Pacific Islander.
- Being
overweight.
- Having high blood pressure.
- Having low
HDL cholesterol (the
“good” cholesterol) and high triglyceride level.
- Being
physically inactive.
- Being age 45
or older.
- Having
gestational diabetes or giving birth to a baby weighing more than 9
pounds.
- Having polycystic ovary syndrome.
- Having a
history of heart disease or stroke.
- Being a
smoker.
Risk factors for gestational diabetes include:
- Family
history (parent or sibling) of Prediabetes or Type 2 diabetes.
- Being
African-American, Hispanic, Native American or Asian-American.
- Being
overweight before your pregnancy.
- Being over
25 years of age.
WHAT CAUSES DIABETES?
Type
1 diabetes
Doctors don’t
know exactly what causes type 1 diabetes. For some reason, the immune system
mistakenly attacks and destroys insulin-producing beta cells in the pancreas.
Genes may
play a role in some people. It’s also possible that a virus sets off the immune
system attack.
Type
2 diabetes
Type 2
diabetes stems from a combination of genetics and
lifestyle factors. Being overweight or obese increases your risk too. Carrying extra weight, especially in your belly, makes your
cells more resistant to the effects of insulin on your blood sugar.
This
condition runs in families. Family members share genes that make them more
likely to get type 2 diabetes and to be overweight.
Gestational
diabetes
Gestational
diabetes is the result of hormonal changes during pregnancy. The placenta
produces hormones that make a pregnant woman’s cells less sensitive to the
effects of insulin. This can cause high blood sugar during pregnancy.
Women who
are overweight
when they get pregnant or who gain too much
weight during their pregnancy are more likely to get gestational diabetes.
The
bottom line
Both genes
and environmental factors play a role in triggering diabetes.
WHAT ARE THE SYMPTOMS OF DIABETES?
Symptoms
of diabetes include:
- Increased
thirst.
- Weak, tired
feeling.
- Blurred
vision.
- Numbness or
tingling in the hands or feet.
- Slow-healing
sores or cuts.
- Unplanned
weight loss.
- Frequent
urination.
- Frequent
unexplained infections.
- Dry mouth.
Other
symptoms
- In women:
Dry and itchy skin, and frequent yeast infections or urinary tract infections.
- In men:
Decreased sex drive, erectile dysfunction, decreased muscle strength
WHAT ARE THE COMPLICATIONS OF DIABETES?
Cardiovascular issues including coronary artery disease, chest pain, heart attack, stroke, high blood pressure, high cholesterol, atherosclerosis (narrowing of the arteries).
Nerve damage (neuropathy) that causes numbing and tingling that starts at toes or fingers then spreads.
Kidney damage (nephropathy) that can lead to kidney failure or the need for dialysis or transplant.
Eye damage (retinopathy) that can lead to blindness; cataracts, glaucoma.
Foot damage including nerve damage, poor blood flow and poor healing of cuts and sores.
Skin infections.
Erectile dysfunction.
Hearing loss.
Depression.
Dementia.
Dental problems
COMPLICATIONS OF GESTATIONAL DIABETES:
·
In
the mother: Preeclampsia (high blood pressure, excess protein in
urine, leg/feet swelling), risk of gestational diabetes during future
pregnancies and risk of diabetes later in life.
·
In
the newborn: Higher-than-normal
birth weight, low blood sugar (hypoglycemia), higher risk of developing Type 2 diabetes
over time and death shortly after birth.
Gestational diabetes
Uncontrolled
gestational diabetes can lead to problems that affect both the mother and baby.
Complications affecting the baby can include:
- premature birth
- higher-than-normal weight at
birth
- increased
risk for type 2 diabetes later in life
- low blood sugar
- jaundice
- stillbirth
The mother can
develop complications such as high blood pressure (preeclampsia) or type 2 diabetes. She may also
require cesarean delivery, commonly referred to as a C-section.
The mother’s risk
of gestational diabetes in future pregnancies also increases.
HOW IS DIABETES DIAGNOSED?
Type
1 DM
Type
1 diabetes: If
your healthcare provider suspects Type 1 diabetes, blood and urine samples will
be collected and tested. The blood is checked for autoantibodies (an autoimmune
sign that your body is attacking itself). The urine is checked for the presence
of ketones (a sign your body is burning fat as its energy supply). These signs
indicate Type 1 diabetes.
Type
2 DM
- Fasting plasma glucose test: This
test is best done in the morning after an eight hour fast (nothing to eat
or drink except sips of water).
- Random
plasma glucose test: This
test can be done any time without the need to fast.
- A1c test: This
test, also called HbA1C or glycated
hemoglobin test, provides your average blood glucose level over
the past two to three months. This test measures the amount of glucose
attached to hemoglobin, the protein in your red blood cells that carries
oxygen. You don’t need to fast before this test.
- Oral glucose
tolerance test: In
this test, blood glucose level is first measured after an overnight fast.
Then you drink a sugary drink. Your blood glucose level is then checked at
hours one, two and three.
|
Type
of test |
Normal |
Prediabetes |
Diabetes |
|
Fasting |
Less than 100 |
100-125 |
126 or higher |
|
Random
(anytime) |
Less than 140 |
140-199 |
200 or higher |
|
A1c test |
Less than 5.7% |
5.7 - 6.4% |
6.5% or higher |
|
Oral glucose |
Less than 140 |
140-199 |
200 or higher |
The current WHO diagnostic criteria for diabetes
– fasting plasma glucose ≥ 7.0mmol/l (126mg/dl) or 2–h plasma glucose ≥
11.1mmol/l (200mg/dl).
Gestational diabetes tests: There are
two blood glucose tests if you are pregnant. With a glucose challenge
test, you drink a sugary liquid and your glucose level is checked one hour
later. You don’t need to fast before this test. If this test shows a higher
than normal level of glucose (over 140 ml/dL), an oral glucose
tolerance test will follow (as described above).
To diagnose gestational diabetes, your doctor
will test your blood sugar levels between the 24th and 28th weeks of
your pregnancy.
- During the
glucose challenge test, your blood sugar is checked an hour after you
drink a sugary liquid.
- During the 3
hour glucose tolerance test, your blood
sugar is checked after you fast overnight and then drink a sugary liquid.
MANAGEMENT
NON-PHARMACOLOGIC
Following a healthy meal plan
Follow a Mediterranean diet (vegetables, whole
grains, beans, fruits, healthy fats, low sugar) or Dash diet. These diets are
high in nutrition and fiber and low in fats and calories.
Eating
the right types of foods can both control your blood sugar and help you lose
any excess weight.
Carb
counting is an important part of eating for type 2 diabetes. A dietitian can
help you figure out how many grams of carbohydrates to eat at each meal.
In
order to keep your blood sugar levels steady, try to eat small meals throughout
the day. Emphasize healthy foods such as:
- fruits
- vegetables
- whole grains
- lean protein
such as poultry and fish
- healthy fats such
as olive oil and nuts
- Exercising regularly. Try to
exercise at least 30 minutes most days of the week. Walk, swim or find
some activity you enjoy.
- Losing weight if you
are overweight.
- Quitting smoking (if
you smoke).
DRUG TREATMENT
Type
1 diabetes
Type 1
diabetes is always treated with insulin injections.
INSULIN
THERAPY
There are four types of insulin that are most commonly used.
They’re differentiated by how quickly they start to work, and how long their
effects last:
- Rapid-acting
insulin starts to work within 15 minutes and its effects last for 3 to 4
hours.
- Short-acting
insulin starts to work within 30 minutes and lasts 6 to 8
hours.
- Intermediate-acting
insulin starts to work within 1 to 2 hours and lasts 12 to 18 hours.
- Long-acting
insulin starts to work a few hours after injection and lasts 24 hours or
longer.
- Rapid-acting
insulins: These insulins are taken 15 minutes
before meals, they peak (when it best lowers blood glucose) at one hour
and work for another two to four hours. Examples include insulin glulisine
(Apidra®), insulin lispro (Humalog®) and insulin aspart (NovoLog®).
- Short-acting
insulins: These insulins take about 30
minutes to reach your bloodstream, reach their peak effects in two to
three hours and last for three to six hours. An example is insulin regular
(Humulin R®).
- Intermediate-acting
insulins: These insulins reach your
bloodstream in two to four hours, peak in four to 12 hours and work for up
to 18 hours. An example in NPH.
- Long-acting
insulins: These insulins work to keep your
blood sugar stable all day. Usually, these insulins last for about 18
hours. Examples include insulin glargine (Basaglar®, Lantus®, Toujeo®),
insulin detemir (Levemir®) and insulin degludec (Tresiba®).
There are insulins that are a combination of
different insulins. There are also insulins that are combined with a GLP-1
receptor agonist medication (e.g. Xultophy®, Soliqua®).
INSULIN ADMINISTRATION
Needle and syringe:
inject the insulin into your belly or thigh,
buttocks or upper arm – rotating the injection spots.
Insulin pen: This device
looks like a pen with a cap. They come prefilled with insulin or with insulin
cartridges that are inserted and replaced after use.
- Insulin pump: Insulin
pumps are small, computerized devices, about the size of a small cell
phone that you wear on your belt, in your pocket, or under your clothes.
They deliver rapid-acting insulin 24 hours a day through a small flexible
tube called a cannula. The cannula is inserted under the skin using a
needle. The needle is then removed leaving only the flexible tube under
the skin. You replaces the cannula every two to three days. Another type
of insulin pump is attached directly to your skin and does not use tubes.
- Artificial
pancreas (also called a closed loop insulin delivery system): This
system uses an insulin pump linked to a continuous glucose monitor. The
monitor checks your blood glucose levels every five minutes and then the
pump delivers the needed dose of insulin.
- Insulin inhaler: Inhalers
allow you to breath in powdered inhaler through an inhaler device that you
insert into your mouth. The insulin is inhaled into your lungs, then
absorbed into your bloodstream. Inhalers are only approved for use by
adults with Type 1 or Type 2 diabetes.
- Insulin
injection port: This delivery method involves the
placement of a short tube into tissue beneath your skin. The port is held
in place with an adhesive patch. You use a needle and syringe or insulin
pen and inject the insulin through this port. The port is changed every
few days. The port provides a single site for injection instead of having
to rotate injection sites.
- Jet
injector: This is a needleless delivery
method that uses high pressure to send a fine spray of insulin through
your skin.
Type 2 diabetes
In most cases, type 2 diabetes treatment
begins with weight reduction through diet and exercise. A healthy diet for a
person with diabetes is low in total calories, free of trans fats and
nutritionally balanced, with abundant amounts of whole grains, fruits and
vegetables, and monounsaturated fats.
Most people with type 2 diabetes need drug
therapy to control blood sugar. However, it is possible to achieve normal blood
sugar levels with weight loss, a healthy diet and regular exercise.
Even if medications are required, diet and
exercise remain important for controlling diabetes.
The medications used for type 2 diabetes
include pills and injections. They work in many different ways. They include
medications that:
·
reduce insulin resistance in the muscles and
liver
·
increase the amount of insulin made and
released by the pancreas
·
provide additional insulin
·
cause a burst of insulin release with each
meal
·
delay the absorption of sugars from the
intestine
·
slow your digestion
·
reduce your appetite for large meals
·
Decrease the conversion of fat to glucose.
|
Types
of drug |
How
they work |
Example(s) |
|
Alpha-glucosidase inhibitors |
Slow your body’s breakdown of sugars
and starchy foods |
Acarbose (Precose)
and miglitol (Glyset) |
|
Biguanides |
Reduce the amount of glucose your liver makes |
Metformin (Glucophage) |
|
DPP-4 inhibitors |
Improve your blood sugar without
making it drop too low |
Linagliptin (Tradjenta), saxagliptin
(Onglyza), and sitagliptin (Januvia) |
|
Glucagon-like peptides |
Change the way your body produces
insulin |
Dulaglutide (Trulicity), exenatide
(Byetta), and liraglutide (Victoza) |
|
Meglitinides |
Stimulate your pancreas to release
more insulin |
Nateglinide (Starlix) and
repaglinide (Prandin) |
|
SGLT2 inhibitors |
Release more glucose into the urine |
Canagliflozin (Invokana) and
dapagliflozin (Farxiga) |
|
Sulfonylureas |
Stimulate your pancreas to release
more insulin |
Glyburide (DiaBeta,
Glynase), glipizide (Glucotrol),
and glimepiride (Amaryl) |
|
Thiazolidinediones |
Help insulin work better |
Pioglitazone (Actos) and
rosiglitazone (Avandia) |
ORAL HYPOGLYCEMIC AGENTS
- Sulfonylureas: These
drugs lower blood glucose by causing the pancreas to release more insulin.
Examples include glimepiride (Amaryl®), glipizide (Glucotrol®) and
glyburide (Micronase®, DiaBeta®).
- Glinides
(also called meglitinides): These drugs lower blood
glucose by getting the pancreas to release more insulin. Examples include
repaglinide (Prandin®) and nateglinide (Starlix®).
- Biguanides: These
drugs reduce how much glucose the liver produces. It also improves how
insulin works in the body, and slows down the conversion of carbohydrates into
sugar. Metformin (Glucophage®) is the example.
- Alpha-glucosidase
inhibitors: These drugs lower blood glucose by
delaying the breakdown of carbohydrates and reducing glucose absorption in
the small intestine. An example is acarbose (Precose®).
- Thiazolidinediones: These
drugs improve the way insulin works in the body by allowing more glucose
to enter into muscles, fat and the liver. Examples include pioglitazone
(Actos®) and rosiglitazone (Avandia®).
- GLP-1
analogs (also called incretinmimetics or glucagon-like peptide-1 receptor
agonists): These drugs increase the release of
insulin, reduce glucose release from the liver after meals and delay food
emptying from the stomach. Examples include exenatide (Byetta®),
liraglutide (Victoza®), albiglutide (Tanzeum®), semaglutide (Rybelsus®) and
dulaglutide (Trulicity®).
- DPP-4
inhibitors (also called dipeptidyl peptidase-4 inhibitors): These
drugs help your pancreas release more insulin after meals. They also lower
the amount of glucose released by the liver. Examples include alogliptin
(Nesina®), sitagliptin (Januvia®), saxagliptin (Onglyza®) and linagliptin
(Tradjenta®).
- SGLT2
inhibitors (also called sodium-glucose cotransporter 2 inhibitors): These
drugs work on your kidneys to remove glucose in your body through your
urine. Examples include canagliflozin (Invokana®), dapagliflozin
(Farxiga®) and empagliflozin (Jardiance®).
- Bile
acid sequestrants: These drugs lower cholesterol and
blood sugar levels. Examples include colestipol (Colestid®),
cholestyramine (Questran®) and colesevelam (Welchol®).
- Dopamine
agonist: This medication lowers the amount of
glucose released by the liver. An example is bromocriptine (Cyclocet®).
Many oral diabetes medications may be used in combination or with
insulin to achieve the best blood glucose control. Some of the above
medications are available as a combination of two medicines in a single pill.
Others are available as injectable medications, for example, the GLP-1 agonist
semaglutide (Ozempic®) and lixisenatide (Adlyxin®).
Gestational diabetes
You’ll need
to monitor your
blood sugar level several times a day during pregnancy. If it’s high, dietary
changes and exercise may or may not be enough to bring it down.
According to the Mayo Clinic, about
10 to 20 percent of women with gestational diabetes will need insulin to
lower their blood sugar. Insulin is safe for the growing baby.
ORAL ANTIDIABETIC AGENTS
|
ORAL HYPOGLYCEMICS |
|
ANTIHYPERGLYCEMICS |
|
Sulfonylureas |
|
Biguanides |
|
Meglitinides |
|
α glucosidase inhibitors |
|
|
|
Thiazolidinediones |
|
|
|
Incretin mimetic |
|
|
|
DPP 4 inhibitors |
|
|
|
Amylin receptor agonists |
Use of Oral Antidiabetic Drugs
•
These agents are indicated in type II
diabetes not controlled by diet & exercise. These are best suited for
patients with:
- Age > 40 at the onset of Dz
- Obesity at the time of presentation.
- Duration of Dz< 5 years when starting Rx.
- FBS < 200mg/ dL
- Insulin requirements < 40U/ day
- No H/O ketoacidosis or any other complications.
I.
SULFONYLUREAS
|
1ST GENERATION |
2nd GENERATION |
|
Tolbutamide |
Glyburide |
|
Chlorpropamide |
Glipizide |
|
|
Gliclazide |
|
|
Glimeperide |
Mechanism of Action
•
Sulfonylurea receptor is present on
ATP sensitive K+ channels on pancreatic β cells.
•
They competitively block the
sulfonylurea receptorÃ
↓ K+ permeability & ↑ Ca++ influx inside the cellsÃ
depolarizationÃ
insulin release.
•
They suppress glucagon levels.
•
↑ in number of insulin receptors on
liver & bind to sulfonylurea
receptors on extrapancreatic cells.
Pharmacokinetics
•
Well absorbed orally.
•
90 to 98 % bound to plasma proteins.
•
Metabolized in liver &/ or kidney.
•
Excreted in urine.
•
Duration of action for 2nd
generation drugs is 10- 24 hours & the onset of action is around 1- 3
hours.
Adverse Effects
•
Hypoglycemia: most important adverse
effect. Can lead to coma. Common in elderly with impaired hepatic & renal
functions.
•
Weight gain occurs due to fluid retention
& edema. Less effective in obese type II diabetic due to accompanying
insulin resistance.
•
Can cross placental barrier & lead
to fetal or neonatal hypoglycemiaÃ
C/I in pregnancy.
•
Chlorpropamide induces a disulfiram
like reaction with alcohol, potentiates ADH & causes cholestatic jaundice.
•
Photosensitivity, rashes, blood
dyscrasias.
•
Nausea, vomiting, flatulence, diarrhea
or constipation, headache, paresthesias occur.
Drug Interactions
•
Drugs that POTENTIATE sulfonylurea
actions:
•
Displace from protein binding:
sulfonamides, salicylates, phenylbutazone, sulfinpyrazone
•
Inhibit metabolism/ excretion:
Cimetidine, acute alcohol intake, warfarin while probenecid& allopurinol
inhibit excretion.
•
Propranolol, sympatholytic
antihypertensives, lithium synergize with sulfonylurea.
•
Drugs that DECREASE
sulfonylurea action:
•
By inducting metabolism:
Phenobarbitone, phenytoin, rifampin, chronic alcohol intake.
•
Opposite action/ suppress insulin
release: OCP, corticosteroids, thiazides, furosemide
II.
Meglitinide
Analogues
•
Quick & short acting insulin
secretion enhancers.
•
Promote insulin secretion from
pancreas by blocking ATP sensitive K+ channels.
•
Administered shortly before meals to
control post prandial rise in blood glucose in type II DM.
•
Skipping or delaying a meal after
meglitinides administration risks hypoglycemia.
•
Repaglinide: Onset of action 1 hour,
duration of action: 4-5 hours. Dose: 0.25-4 mg orally before each meal. S/E:
headache, dyspepsia, indigestion.
•
Nateglinide: Onset of action 1 hour,
duration of action: 4-5 hours. Dose: 60-120 mg before each meal. S/E:
dizziness, nausea, flu symptoms.
•
These drugs cause lesser weight gain
and are lesser allergenic than sulfonylureas. Can be combined with biguanides.
III.
Biguanides
•
Metformin &Phenformin
•
Phenformin no longer used as it caused
lactic acidosis.
•
Metformin currently in used drug in
these class.
•
M/A: Does
not depend on functional β cells as it does not cause insulin release
from pancreasÃ
no risk of hypoglycemia.
Mechanism of Action
•
Metformin ↑ uptake & utilization
of glucose by skeletal musclesÃ
↓ insulin resistance.
•
↓ hepatic& renal gluconeogenesisà ↓ hepatic
glucose output.
•
Slowing glucose absorption by
enterocytes which ↑ availability of glucose for its conversion to lactate.
•
Promotion of insulin binding to its
receptors.
•
Metformin causes anorexiaà drug of
first choice in obese type II diabetics.
•
Lowers VLDL & LDL & increases
HDL levels.
•
Clinical Uses:
•
In type II obese diabeticsà DoC
•
To treat insulin resistance syndrome,
it can be combined with sulfonylureas, meglitinides&glitazones.
•
Metformin therapy ↓ the risk of micro
& macrovascular complications of the disease.
•
Dose 500 mg BD before breakfast &
dinner.
•
Metformin ↓ androgen levels &
enhance insulin sensitivity in PCODÃ
used to treat hirsutism& enhance fertility in these women.
•
Plasma t1/2= 2-3 hours. Duration of
action 6-10 hours. Excreted unchanged in urine.
Adverse Effects
•
Nausea, metallic taste, flatulence,
diarrhea
•
Long term Rx may ↓ absorption of vit.
B12.
•
Patients with renal, hepatic, hypoxic
lung Dz& heart failure are predisposed to lactic acidosis due to reduced
drug elimination or reduced tissue oxygenation.
•
Alcohol ingestion can also precipitate
lactic acidosis.
IV.
α
Glucosidase Inhibitors
•
Acarbose, voglibose&miglitol
•
Disaccharides & oligosaccharides
are broken down by the enzyme αglucosidase to monosaccharides which are
absorbed from the small intestine.
•
Thus these drugs reduce post prandial
absorption of glucose by competitively inhibiting αglucosidase causing hypoglycemia.
•
With regular use, they reduce HbA1c,
body weight & serum triglycerides.
•
Acarbose is minimally absorbed. Some
part excreted through feces while some part metabolized by intestinal flora.
•
Dose: 50-100 mg TDS before meals.
•
Used as monotherapy in early type II
diabetes & with sulfonylureas in obese diabetics.
•
Adverse Effects:
•
Flatulence, diarrhea, abdominal pain.
•
Contraindicated in intestinal
obstruction & inflammatory bowel disease.
•
Do not cause hypoglycemia when used
alone.
•
If hypoglycemia occurs, it should be
corrected by glucose & not sucrose as its breakdown is already
blocked by these drugs.
V.
Thiazolidinediones
(Glitazones)
•
Rosiglitazone & pioglitazone
•
M/A:
•
Acts as agonist to PPAR γ receptor
expressed in adipose tissue, skeletal muscle & liver.
•
Activation PPAR γÃ
insulin responsive genes transcription which control glucose & lipid
metabolismÃ
↑ insulin sensitivity & ↓ insulin resistance in type II DM.
•
↑ the number of GLUT 4 transporters in
skeletal muscles & adipose tissueÃ
promotes peripheral glucose uptake & utilization.
•
Inhibit gluconeogenesisà ↓ hepatic
glucose output.
•
↑ HDL & lower triglyceride &
HbA1c levels.
•
Mainly beneficial in type II diabetics
with substantial insulin resistance. Insulin sensitizing action takes several
weeks to develop.
•
Adverse Effects:
•
Weight gain due to fluid retention
& edema.
•
↑ deposition of subcutaneous fat &
ECFÃ hemodilution&
hence ↓ Hb concentration.
•
Rare incidences of hepatotoxicity.
Monitor LFTs.
•
C/I in hepatic failure, pregnancy
& lactation, in children & heart failure patients.
•
Rosiglitazone recently withdrawn due
to possible ↑ in risk of MI & heart failure.
Novel Antidiabetic Drugs
Incretin
Physiology
•
Incretin hormones: Glucagon Like
Peptide- 1 (GLP 1) & Glucose Dependent Insulinotropic Polypeptide (GIP).
•
These are released from intestine
after a meal.
•
Augment glucose dependent insulin
secretion.
•
GLP 1 is metabolized by Dipeptidyl
Peptidase IV (DPP IV) enzyme & thus has a t1/2 1-2 mins.
•
These incretins have been the target
for novel approaches in treatment of DM type II.
GLP
1 AGONISTS
·
Exenatide:
Synthetic analog of Exendin4 which is a potent GLP 1 agonist. Orally inactive.
Given SC. Decrease blood glucose and reduces weight.
·
Exendin 4
is derived from venom of gila monster.
Dose: 5-10 microgram/day
S/E:
Nausea, vomiting, anorexia, diarrhea, rarely necrotizing pancreatitis, antibody
formation and increase B cell mass.
M/A
of Exenatide:
•
Stimulates insulin secretion from
pancreas.
•
Decrease glucagon release
•
Decreases appetite by acting at the
level of hypothalamic feeding center & thus reduces weight.
•
Used in combination with sulfonylureas
or Metformin in resistant type II DM.
DIPEPTIDYL PEPTIDASE IV INHIBITORS
•
Sitagliptin,
Saxagliptin&Vildagliptin
• Orally
active inhibitors of DPP IVÃ
prolongs T1/2 of GLP 1 which thus:
- ↑ insulin release.
- ↓ glucagon release.
- Delay gastric emptying.
- Suppress appetite.
•
Used in combination with sulfonylureas
or Metformin in resistant type II DM.
Pharmacokinetics
•
T1/2: 8-14 hours.
•
Route of administration: Oral
•
Hepatic metabolism & renal
excretion
•
Dose: 100mg/day
•
Not associated with weight gain or
hypoglycemia.
•
S/E: stuffy runny nose, headache, sore
throat &nasopharyngitis (due to substance P elevation), GI distress &
diarrhea.
SYNTHETIC
AMYLIN ANALOGE
•
Amylin is a neuroendocrine peptide
secreted with insulin. Amylin leads to:
1.
Decrease endogenous glucagon
production.
2.
Decrease PP glucose output from liver.
3.
Central mediator of satiety.
4.
Inhibits orexigenic hormone ghrelin.
•
PRAMLINTIDE is a modified amylin
peptide which is an agonist at amylin receptors.
•
Dose:
30-120 micrograms subcutaneous.
•
S/E:
Nausea, vomiting, anorexia, diarrhea, head- ache.
TRANSPLANTATION
For
a select number of patients who have Type 1 diabetes. A pancreas
transplant is possible. However, getting an organ
transplant requires taking immune-suppressing drugs for the rest of your life
and dealing with the side effects of these drugs. However, if the transplant is
successful, you’ll likely be able to stop taking insulin.
Another type of transplant is a pancreatic islet transplant.
In this transplant, clusters of islet cells (the cells that make insulin) are
transplanted from an organ donor into your pancreas to replace those that have
been destroyed
Another treatment under research for Type 1 diabetes is immunotherapy.
Since Type 1 is an immune system disease, immunotherapy holds promise as a way
to use medication to turn off the parts of the immune system that cause Type 1
disease.
Bariatric surgery is another treatment option that’s an indirect
treatment for diabetes. Bariatric surgery is an option if you have Type 2
diabetes, are obese (body mass index over 35) and considered a good candidate
for this type of surgery. Much improved blood glucose levels are seen in people
who have lost a significant amount of weight.
MEDICATIONS FOR
CO-MORBIDITIES
These conditions include high blood pressure, high cholesterol and other
heart-related diseases
PREVENTION
Simple
lifestyle measures have been shown to be effective in preventing or delaying
the onset of type 2 diabetes. To help prevent type 2 diabetes and its
complications, people should:
- achieve and maintain a healthy body
weight;
- be physically active – doing at least 30
minutes of regular, moderate-intensity activity on most days. More
activity is required for weight control;
- eat a healthy diet, avoiding sugar and
saturated fats; and
- Avoid tobacco use – smoking increases the
risk of diabetes and cardiovascular disease.
Prediabetes, Type 2 diabetes and gestational diabetes
Deal
with modifiable risk factors:
Eat
a healthy diet
Get
physically active. Aim for 30 minutes a day at least five days a week.
Lose
weight if you are overweight
Lower your stress. Learn
relaxation techniques, deep breathing exercises, mindful meditation, yoga and
other helpful strategies.
Limit alcohol intake. Men should drink no more
than two alcoholic beverages a day; women should drink no more than one.
Get an adequate amount of sleep (typically
7 to 9 hours).
Quit smoking.
Take medications – to manage existing risk
factors for heart disease (e.g., high blood pressure, cholesterol) or to reduce
the risk of developing Type 2 diabetes – as directed by your healthcare
provider.
Type 1 diabetes
Cannot
be prevented; it is an autoimmune disease
HYPOGLYCEMIA
BS usually below 70 mg/dL is
called hypoglycemia
- Weakness or
shaking.
- Moist skin,
sweating.
- Fast
heartbeat.
- Dizziness.
- Sudden
hunger.
- Confusion.
- Pale skin.
- Numbness in
mouth or tongue.
- Irritability,
nervousness.
- Unsteadiness.
- Nightmares,
bad dreams, restless sleep.
- Blurred
vision.
- Headaches,
seizures.
- A blood
glucose level greater than 125 mg/dL while in the fasting state (nothing
to eat or drink for at least eight hours).
or
- A blood
glucose level greater than 180 mg/dL one to two hours after eating.