This document provides information about diabetes mellitus (DM), including the types, causes, symptoms, treatment, and complications. It discusses: 1) The two main types of DM - type 1 (insulin dependent) and type 2 (non-insulin dependent). Type 2 represents 90% of cases and is associated with obesity. 2) The metabolic effects of DM including alterations in carbohydrate, protein, and fat metabolism that can lead to hyperglycemia, glucosuria, ketosis, and complications affecting multiple organ systems. 3) Long-term vascular complications of DM including microangiopathy affecting small blood vessels (retinopathy, nephropathy) and macroangiopathy affecting

1. Prepared by pharmacist/ Mohamed
Adel
Graduate of zagazig university 2016

2. Diabetes mellitus (DM) is a syndrome with metabolic
and vascular disorders which result from;
1-insulin insufficiency "decrease the insulin release".
2-insulin receptors insufficiency "unresponsiveness".
3-decrease the number of receptors.
4-defect in β-cells or insulin itself.
5-removal of pancreas.

3. 1-autoimmune reaction leads to the destruction of β-
cells.
2-heredity
3-viral infection affecting the pancreas.
4-secodary to drugs and stress.
5-obestiy causes insulin resistance.
Symptoms;
1-hyperglycemia and glucosuria.
2-3p; polyuria, polyphagia and polydipsia.
3-fatigue and visual disturbance.
4-dehydration, loss of body weight and weakness.

4. 1-type 1 diabetes mellitus (juvenile diabetes) or insulin
dependent diabetes mellitus (IDDM)
It represents only 10% of the cases. Due to autoimmune disease or
viral infection of pancreas with genetic predisposition.
It is characterized by absolute insulin deficiency. It appears in
children most patients are younger than 30 years of age and ttt by
insulin only.
2-type 2 diabetes mellitus (maturity onset) or non-
insulin dependent diabetes mellitus (NIDDM)
It represent 90% of the cases of DM. it is associated with obesity.
It is characterized by insulin insensitivity(tissue resistance) or
relative insulin deficiency (inadequate to overcome the resistance),.
It appear in adults in the age of 35-45 years and ttt by oral
hypoglycemic, insulin sensitizer and insulin.

5. 3-genetic diabetes of β-cell function
a-mitochondrial DNA defects.
b-maturity onset diabetes of young (MODY);
appear before and at the age of 25 years due to mutation at glucokinase enzyme so
no glucose transformed to G-6-P (1ry cause of diabetes.
4-endocrinopathies this type refers to multiple other specific causes of an
elevated blood glucose: pancreatectomy, pancreatitis, non pancreatic diseases due
excessive secretion of glucocorticoids, GH and catecholamine (anti-insulin
hormones).
5-drug-induced diabetes this type due to administration of some drugs
that interfere with insulin secretion like thiazides, phenytoin, β-adrenergic
antagonists, Diazoxides.
6-Gestational diabetes is a condition in which the blood sugar levels
become high during pregnancy usually disappears after giving birth. It
happens when your body cannot produce enough insulin to meet extra
needs in pregnancy. Risks; polyhydramnios –premature birth –
preclampsia
Screening may be deferred until the 24th to 28th week of gestation..

6. Chemistry
It contains 51 amino acids arranged in two chains (A and B) linked by disulfide bridges; there
are species differences in the amino acids of both chains.
Insulin Secretion
Insulin is released from in response to stimuli, especially glucose. Other stimulants
such as other sugars (eg, mannose),
amino acids (especially gluconeogenic amino acids, eg, leucine, arginine),
hormones such as glucagon-like polypeptide-1 (GLP-1), glucose-dependent
insulinotropic polypeptide (GIP), glucagon, cholecystokinin, high concentrations of
fatty acids, and -adrenergic sympathetic activity are recognized.
Stimulatory drugs , isoproterenol, and acetylcholine.
Inhibitory signals are hormones including insulin itself and leptin,  -adrenergic
sympathetic activity,
chronically elevated glucose, and
low concentrations of fatty acids.
Inhibitory drugs include diazoxide, phenytoin, vinblastine and colchicine.
hyperglycemia →↑ intracellular ATP levels, → close the ATP-dependent
potassium channels. → in depolarization of the beta cell→opening of voltage-
gated calcium channels. →↑intracellular calcium→insulin..

8. Effect on liver:
Reversal of catabolic features of insulin deficiency Inhibits
glycogenolysis/ Inhibits conversion of fatty acids and amino acids to keto
acids/ Inhibits conversion of amino acids to glucose
Anabolic action Promotes glucose storage as glycogen (induces
glucokinase and glycogen synthase, inhibits phosphorylase) /Increases
triglyceride synthesis and very-low-density lipoprotein formation
Effect on muscle:
Increased protein synthesis Increases amino acid transport/Increases
ribosomal protein synthesis
Increased glycogen synthesis Increases glucose transport/Induces
glycogen synthase and inhibits phosphorylase
Effect on adipose tissue:
Increased triglyceride storage Lipoprotein lipase is induced and
activated by insulin to hydrolyze/triglycerides from
lipoproteins/Glucose transport into cell provides glycerol phosphate to
permit esterification of fatty acids supplied by lipoprotein
transport/Intracellular lipase is inhibited by insulin

9. DM is characterized by metabolic and vascular
disorders;
a-metabolic syndrome(acute effects); characterized
by alteration in CHO, protein and fat metabolism.
b-vascular syndrome(late complication of DM);
abnormalities in both small(microanigopathy) and
large blood vessels (macroangiopathy).

10. Metabolic syndrome; characterized by alteration in CHO, protein and
fat metabolism.
1-alteration in CHO metabolisms
1-normal blood glucose level (70-110) mg/dl. Normally glucose enters
the cell for glycolysis by the help of insulin and so converted to
glycogen in liver and skeletal muscles.
2-in case of DM; acute insulin deficiency→ the glucose not utilized by
the body and not converted to glycogen leads to
1) hyperglycemia (↑ blood glucose level ) that exceeds the renal sugar
threshold for reabsorption (180mg/dl) →glucosuria (presence of
glucose in urine) →↑ glucose in urine →↑osmotic pressure→ withdraw
fluids with urine →↑urination (polyuria) specially at night→ loss of
electrolytes →dehydration→ thirst (polydipsia) →hyperglycemic
coma.
2) ↑ glycogen breakdown and gluconeogenesis in liver→
hyperglycemia then same sequence.
3) ↑osmotic pressure (osmolality) → withdraw fluids with urine
→dehydration →coma

11. 2-alteration in fat metabolisms
- Acute insulin deficiency→ lipolysis (body will use fats to
produce energy instead of glucose due to its high energy leads
to:
1)weight loss.
2) acetyl CoA→ kerp's cycle→ gluconeogenesis→ ↑energy.
3)ketones body formation in liver (acetone-acetoacetate- β-
butyric acid) →ketosis (presence of ketone bodies in blood, urine
and breath) →↓PH of the blood also by presence of fatty acids
→metabolic acidosis→ destruction of vital organs (brain-heart)
due to dehydration → hyperglycemic coma then death.
4)metabolic acidosis→ (Kussmaul breathing is a deep and
labored breathing pattern and form of hyperventilation to
↓acidosis).
5)fruit-lozenge breath & fatty liver& failure of kidney →acidosis
(as capacity to restore normal PH ↓) → loss of electrolyte.

14. 3-alteration in protein metabolism
acute insulin deficiency→ proteolysis (body will use proteins to
produce energy instead of glucose due to its high energy and
leads to:
1) weight loss.
2)↑ amino acids → acetyl CoA(Amino acids that are degraded to
acetyl CoA or acetoacetyl CoA) → kerp's cycle→
gluconeogenesis→ ↑energy.
3)↑ amino acids that exceeds the renal sugar threshold for
reabsorption→ aminoaciduria (presence of amino acids in urea)
high glucose in urine →↑osmotic pressure→ withdraw fluids
with urine →↑urination (polyuria) specially at night→ loss of
electrolytes →dehydration→ thirst (polydipsia) →coma.
4) ↑ acetyl CoA→ kerp's cycle→ gluconeogenesis→↑ glucose level
→↑osmotic pressure→ withdraw fluids→ dehydration→ coma.

15. b-vascular syndrome(late complication of DM); abnormalities in
both small(microanigopathy) and large blood vessels
(macroangiopathy).
1-macroangiopathy
They are abnormalities in the large blood vessels.e.g.
Atherosclerosis is the most common macrovacular complication
of diabetes and ↑the risk for stroke, myocardial infarction and
peripheral artery disease→limb amputation due the neuropathy
(decrease the nerve supply) and↓blood supply so ↓nutrients and
leucocytes so cause infection and slowing healing process.
2-microanigopathy
They are abnormalities in the small blood vessels. E.g.
microvascular complications cause retinopathy and nephropathy
→blindness and renal failure due to damage in fine capillaries in
nephron and retina.

16. 1-Retinopathy Persistent glucose excess (hyperglycemia)
→↑sorbitol by the enzyme aldose reductase & cannot cross cell
membranes, and when it accumulates → drawing water into the
cell→ osmotic swelling and stress in eye and kidney and neurons.
↑sorbitol →↓ the cellular myoinositol uptake→↓ the activity of the
plasma membrane Na+/K+ ATPase pump required for nerve
function→ impaired nerve conduction→ polyneuropathy
(↓autonomic nervous regulation-↓reflexes -↓sensory response) also
may affect the nerves in retina →retinopathy →blindness.
↑ Sorbitol → accumulation→ osmotic changes resulting in hydropic
lens fibers that degenerate → cataracts (opacities) lens (a collapse
and liquefaction of lens fibers and due to the extensive swelling of
cortical lens fibers).
↑ Sorbitol → accumulation→ osmotic stress in the endoplasmic
reticulum→ the generation of free radicals reactive oxygen
species (ROS) →oxidative stress damage to lens fibers→
retinopathy.

17. ↑ glucose levels(sorbitol) → activate biochemical pathway→ ↓
glutathione and ↑reactive oxygen radicals→ oxidative
stress→↓Glutathione in retina..
↑glucose levels in the aqueous humor → glycosylation of lens
proteins→ generation of superoxide radicals and →formation of
advanced glycation end products (AGE).
By interaction of AGE with cell surface receptors such as
receptor for advanced glycation end products in the
epithelium of the lens further and H2O2 are generated→
oxidative stress damage to lens fibers→ retinopathy
Persistent glucose excess (hyperglycemia) →glycosylation of
the protein then alters their structure and inhibits their
function in the endothelial cells →↑thickening of the basal
membrane→ microangiopathy (abnormalities is small blood
vessels)→↓blood flow → diminished oxygen tension and
hypoxia→ damage to nerves retina (as Blood vessels depend
on normal nerve function, and nerves depend on adequate
blood flow.) →retinopathy.
.

18. 2-Neuropathy
Persistent glucose excess (hyperglycemia) →↑sorbitol by the enzyme aldose
reductase & cannot cross cell membranes, and when it accumulates →
drawing water into the cell→ osmotic swelling and stress in eye and kidney
and neurons.
↑sorbitol →↓ the cellular myoinositol uptake→↓ the activity of the plasma
membrane Na+/K+ ATPase pump required for nerve function→ impaired
nerve conduction→ polyneuropathy (↓autonomic nervous regulation-
↓reflexes -↓sensory response)
3-Nephropathy
Persistent glucose excess (hyperglycemia) →↑hyper-osmolarity → prone to
infection→ pyelonephritis (necrotizing infection of the body of the kidney
that may spread to the Para renal areas) →renal failure→ hypertension→
macroangiopathy .
Persistent glucose excess (hyperglycemia) →↑hyperosmolarity →
gomerulosclerosis→ renal failure→ hypertension→ macroangiopathy.
Macroangiopathy→ stroke or myocardial infarction or peripheral vascular
disease or placental perfusion or renal failure

19. 4-Blood vessels
Persistent glucose excess (hyperglycemia)
→glycosylation of the protein→↑fibrinogen,
haptoglobin, clotting factors V and VIII →↑blood
clotting and viscosity→ macroangiopathy.
Persistent glucose excess (hyperglycemia)
→glycosylation of the protein then alters their
structure and inhibits their function in the
endothelial cells →↑thickening of the basal
membrane→ macroangiopathy.

20. 1-blood sugar level (random and fasting).
2-oral glucose tolerance test (oral GIT) the best
detect the metabolism for glucose.
3-insulin level test.
4-C-peptide level.
5-glycated or glycosylated hemoglobin "Hb" not
appear otherwise patient is with hyperglycemia not
less than 1-2 months.

21. 1-diet control and adequate individualized diet
(↓CHO consumption).
2-approporiate regular exercises.
3-realstic body weight reduction (obesity should
reduce as →resistance of receptors to insulin).
4-drugs→diabetes →hypertension.

22. 1-insulin
(IV Hypoglycemic as insulin is clear so used IV) &
metabolized in liver by specific protease enzyme
(insulinase) and it is also cleared by peripheral
tissues and kidney.
insulin is peptide that is destroyed by digestive enz
so it is ineffective or inactive orally.
2-oral hypoglycemic drugs.

23. Ch.chDurationOnsetExamplesTypes of insulin
Clear at
neutral ph
3-5 hr5-15 minLispro(humalog)
Aspart (novolog)
Glulisine (humalog)
1-Ultra
short(rapid)
acting
Clear at
neutral ph
6— 8 hr30 —45
min
Regular insulin e.g humulin
R ,Novolin R
2-short acting
Trubid soln13—20hr1—3hrIsophane (NPH) neutral
protamine hagedorn in
phosphate buffer e.g
humulin N , Novolin N
Lente mixture of semilente
and ultralente e.g novolin L ,
Humulin L
3-intermediate
acting
Clear but ppt
at injection
long 24hrslow
upto 2hr
Glargine (lantus)
Detemir (levemir)
Degludec (tresiba)
. 4-long acting
intermediate insulins composed of
isophane complexes of protamine with
insulin lispro and insulin aspart have
been developed. “NPL” (neutral
protamine lispro) and “NPA” (neutral
protamine aspart) and have the same
duration of action as NPH insulin.
Novolin 70 NPH/30 regular
Humulin 70 NPH/30
regular
75/25 NPL, Lispro
70/30 NPA, Aspart
5-Premixed
insulin

24. 1-Ultra short(rapid) acting
Insulin lispro two amino acids near the carboxyl terminal of
the B chain have been reversed in position: Proline at
position B28 has been moved to B29, and lysine at position
B29 has been moved to B28 the advantage of this analog is its
very low propensity to self associate in antiparallel fashion
and form dimers.
To enhance the shelf life of insulin in vials, insulin lispro is
stabilized into hexamers by a cresol preservative, then drug
quickly dissociates into monomers and is rapidly absorbed
Insulin aspart is created by the substitution of the B28
proline with a negatively charged aspartic acid.
This modification reduces the normal ProB28 and GlyB23
monomer-monomer interaction, thereby inhibiting insulin
self-aggregation.
Insulin glulisine is formulated by substituting a lysine for
asparagine at B3 and glutamic acid for lysine at B29.

25. 2. Short-acting insulin
Regular insulin is a soluble crystalline zinc insulin that is now
made by recombinant DNA techniques to produce a molecule
identical to that of human insulin.
In high concentrations, eg, in the vial, regular insulin molecules
self-aggregate in antiparallel fashion to form dimers that
stabilize around zinc ions to create insulin hexamers.
The hexameric nature of regular insulin causes a delayed onset
and prolongs the time to peak action.
After subcutaneous injection, the insulin hexamersare too large
and bulky to be transported across the vascular endothelium
into the bloodstream.
As the insulin depot is diluted by interstitial fluid →dimers
→monomers.

26. 3. Intermediate-acting and long-acting insulin
NPH (neutral protamine Hagedorn, or isophane) NPH insulin is an
intermediate-acting insulin whose absorption and onset of action are
delayed by combining appropriate amounts of insulin and protamine
so that neither is present in an uncomplexed form (“isophane”).
After subcutaneous injection, proteolytic tissue enzymes degrade the
protamine to permit absorption of insulin.
4. long-acting and long-acting insulin
Insulin glargine created by The attachment of two
arginine molecules to the B-chain carboxyl terminal and substitution
of a glycine for asparagine at the A21 position.
Insulin detemir— This insulin is the most recently developed
long-acting insulin analog. The terminal threonine is dropped
from the B30 position and myristic acid (a C-14 fatty acid chain)
is attached to the terminal B29 lysine. These modifications prolong
the availability of the injected analog by increasing both
self-aggregation in subcutaneous tissue and reversible albumin
binding.

27. 5. Mixtures of insulin
Because intermediate-acting NPH insulin require several
hours to reach adequate therapeutic levels, their use in
diabetic patients usually requires supplements of
rapid- or short-acting insulin before meals
intermediate insulin composed of isophane complexes of
protamine with insulin lispro and insulin aspart have been
developed.
premixed preparations have thus far been unstable. So
These intermediate insulins have been designated as “NPL”
(neutral protamine lispro) and “NPA” (neutral
protamine aspart) and have the same duration of action as
NPH insulin. They have the advantage of permitting
formulation as premixed combinations of NPL and insulin
lispro, and as NPA and insulin aspart.

29. total daily insulin requirement(TDI) =0.3-0.6 unit /kg /day
The common used 0.5 unit/kg/day.
Example; patient 60 kg so the number of his insulin unit=0.5*60=30unit
per day so monthly=30*30=900unit.
The volume capacity(the number of unit) of insulin vial and cartilage or
pen-fill;
The volume capacity of vial=1000unit
The volume capacity of cartilage or pen-fill =300unit
The insulin daily regimen for types and doses:
1-Basal -bolus insulin dosing( long-acting/ultra-short)
2-twice daily or Regular /NPH regimen(intermediate/short).
N.P. basal insulin like NPH.
regular insulin like ultra-short.

30. 1-Basal -bolus insulin dosing
Two types of insulin and the percentage to each
other 50-50%;
The total daily insulin requirement
Basal insulin
50% total daily
requirement
This type along the day not
related to meals
Long acting insulin
Glargine (lantus)
Detemir (levemir)
Degludec (tresiba)
Taken at night
bolus insulin
50% total daily requirement
Related to meals
Ultra short acting
Lispro(humalog)
Aspart (novolog)
Glulisine (humalog)
Divided on 3 the no of meals
Taken 5-15-mins before each meal

31. 2-twice daily or Regular /NPH regimen.
Two types of insulin and the ratio to each other
2/3-1/3;
Morning dose insulin
2/3 total daily
requirement
Morning dose divided by
2/3 &1/3 into
Evening dose insulin
1/3 total daily requirement at6
pm.
2/3 intermediate insulin,
Isophane (NPH) neutral
protamine hagedorn in
phosphate buffer e.g
humulin N , Novolin N
Lente mixture of
semilente and ultralente
e.g novolin L , Humulin L
1/3short
acting
insulin,
Regular
insulin e.g
humulin R
,Novolin R
2/3 intermediate
insulin, Isophane
(NPH) neutral
protamine hagedorn
in phosphate buffer
e.g humulin N ,
Novolin N
Lente mixture of
semilente and
ultralente e.g novolin
L , Humulin L
1/3short
acting insulin,
Regular
insulin e.g
humulin R
,Novolin R

32. basal insulin act like NPH.
ultra-short act like regular insulin.
NPH to insulin glargine (lantus) =80%of NPH unit
NPH to detemir (levemir) = the same NPH unit
Regular to bolus AKA Ultra short acting e.g.
Lispro(humalog) or Aspart (novolog) or Glulisine
(humalog) =the same Regular unit then divided by
3(no of meals)

33. 1-If the patient has a high blood glucose level in morning before
meal (fasting) so the error will be in the basal insulin( long acting
insulin) or NPH, then the correction will be 1 unit for every day or 2
unit for every 3 days.
2-If the patient has a high blood glucose level 2 hrs after the meal, so
the error will be in the bolus (rapid or short) insulin, then the
correction will be
according to correction factor CF =sensitivity factor correctional
insulin needs according to the type of used insulin;
Rapid insulin e.g. aspart or lispro or Glulisine =1800/TDI
Short acting insulin e.g. regular =1500/TDI.
Then after obtaining the correction factor CF , calculate the increase
in blood glucose level from the normal(X)
X= (high or increased glucose level) – (normal glucose level)
Divide the X by correction factor CF =X/CF=the no of unit needed
to add from the used type of insulin.

34. A. Hypoglycemia
result from inadequate carbohydrate consumption, unusual physical
exertion, or too large a dose of insulin.
signs tachycardia, palpitations, sweating, tremulousness, nausea,
hunger and may progress to convulsions and coma if untreated.
Treatment of hypoglycemia—by glucose administration to a conscious
patient, form of rapidly absorbed glucose, should be carried by every
diabetic person who is receiving hypoglycemic
drug therapy.
If unconscious patient, the treatment of choice is to give 20–50 mL of
50% glucose solution by intravenous infusion over a period of 2–3
minutes.
If intravenous therapy is not available, 1 mg of glucagon injected either
subcutaneously or intramuscularly may restore consciousness within
15 minutes to permit ingestion of sugar.
Emergency medical services should be called immediately for all
episodes of severely impaired consciousness..

35. B. Immunopathology of Insulin Therapy
1. Insulin allergy
Insulin allergy, an immediate type hypersensitivity,
is a rare condition in which local or systemic urticaria
results from histamine release from tissue mast cells
sensitized by anti-insulin IgE antibodies. In severe
cases, anaphylaxis results.
2. Immune insulin resistance
A low titer of circulating IgG anti-insulin antibodies
that neutralize the action of insulin to a negligible
extent develops in most insulin-treated patients.
Rarely, the titer of insulin antibodies leads to insulin
resistance and may be associated with other systemic
autoimmune processes such as lupus erythematosus.

36. C. Lipodystrophy at Injection Sites
Hypertrophy of subcutaneous fatty tissue remains a
problem if injected repeatedly at the same site.
However, this may be corrected by avoiding the
specific injection site or by liposuction.
D. Increased Cancer Risk
An increased risk of cancer attributed to insulin resistance
and hyperinsulinemia has been reported in individuals with
insulin resistance, prediabetes, and type 2 diabetes.
Treatment with insulin and sulfonylureas, which increase
circulating insulin levels,

38. A. Insulin Secretagogues
sulfonylurea drugs
1st generation; Tolbutamide, chloropropamide
older sulfonylurea drugs, lower potency, greater toxicity;
rarely used are extensively bound to serum proteins, and
drugs that compete for protein binding may enhance their
hypoglycemic effects
2nd generation; Glyburide, glimepiride, glipizide
intermediate duration of action
Meglitinide Repaglinide and nateglinide
fast-acting insulin secretagogues useful for administration
just before a meal to control postprandial glucose levels.
Moa; Increases insulin secretion from pancreatic beta cells
by closing ATP-sensitive K+ channels
S/E; Hypoglycemia, weight gain(patients with type 2
diabetes who already are overweight).

40. B. Biguanides
Metformin
Moa Decreased endogenous glucose production through
1-Biguanides inhibit hepatic and renal gluconeogenesis.
2-stimulation of glucose uptake and glycolysis in peripheral
tissues.
3-slowing of glucose absorption from the gastrointestinal tract,
4-reduction of plasma glucagon levels.
In patients with insulin resistance(overweight with DM2T )
through enhanced insulin sensitivity not increase weight. Or cause
hypoglycemia.
Metformin is also used to restore fertility in anovulatory women
with polycystic ovary disease (PCOD)
S/E, gastrointestinal distress (nausea, diarrhea), lactic acidosis,
especially in patients with renal or liver disease, alcoholism, or
conditions that predispose to tissue anoxia and lactic acid
production (eg, chronic cardiopulmonary dysfunction).

41. C. Thiazolidinediones
rosiglitazone and pioglitazone
Roglitazone was removed from the market in several countries
because of hepatotoxicity (increased risk of MI).
MOA increase target tissue sensitivity to insulin
by activating the peroxisome proliferator-activated receptor-gamma
nuclear receptor (PPAR-γ receptor) regulates the transcription of genes
encoding proteins involved in CHO and lipid metabolism through
1-increasing glucose uptake in muscle and adipose tissue .
2-They also inhibit hepatic gluconeogenesis
3-effects on lipid metabolism and the distribution of body fat.
S/E, Fluid retention, edema, anemia, weight gain, bone
fractures in women, may worsen heart disease and increase risk of
myocardial infarction
induce cytochrome P450 activity (especially the CYP3A4 isozyme) and
can reduce the serum concentrations of drugs that are metabolized by
these enzymes (eg, oral contraceptives, cyclosporine).

42. D. Alpha-Glucosidase Inhibitors
Acarbose and miglitol
MOA, are carbohydrate analogs inhibit Alpha-Glucosidase ,
so inhibit the conversion of oligosaccharides, and
disaccharides to the monosaccharide that can be
transported out of the intestinal lumen and into the
bloodstream. As a result of slowed absorption, postprandial
hyperglycemia is reduced.
S/E, flatulence, diarrhea, and abdominal pain resulting
from increased fermentation of unabsorbed carbohydrate
by bacteria in the colon.
Patients taking an α-glucosidase inhibitor who experience
hypoglycemia should be treated with oral glucose
(dextrose) and not sucrose, because the absorption of
sucrose will be delayed.

43. E. Amylin analog,
Pramlintide
MOA, Analog of amylin(a 37-amino acid hormone
produced by pancreatic B cells). activates amylin
receptors
Amylin contributes to glycemic control by activating
high-affinity receptors involved in both glycemic
control.
Pramlintide suppresses glucagon release, slows
gastric emptying, and works in the CNS to reduce
appetite.
S/E, hypoglycemia and gastrointestinal
disturbances.

44. F.Incretin modulators
1-GLP-1 analog (exenatide)
MOA, Analog of glucagon-like peptide-1 (GLP-1)
activates GLP-1 receptors Glucagon-like peptide-1 (GLP-1) is a
member of the incretin family of peptide hormones, which are
released from endocrine cells in the epithelium of the bowel in
response to food.
The incretins augment glucose-stimulated insulin release from
pancreatic B cells, retard gastric emptying, inhibit glucagon
secretion, and produce a feeling of satiety.
S/E, GI disturbances, headache, pancreatitis
2-DPP-4 inhibitor (sitagliptin, saxagliptin, linagliptin, and
alogliptin)
MOA Inhibitor of the dipeptidyl peptidase-4 (DPP-4) that
degrades GLP-1 , prolong the DOA of GLP-1 so promotes insulin
release, inhibits glucagon secretion,
S/E, Rhinitis, nasopharyngitis, upper respiratory infections, rare
allergic reactions.

45. G. The sodium-glucose transporter 2(SGLT2)
inhibitors
canagliflozin , dapagliflozin and empagliflozin
MOA, Inhibit renal glucose absorption via SGLT2
& its inhibition causes glycosuria and lowers
glucose levels.
S/E, Osmotic diuresis intravascular volume
contraction and hypotension., genital and urinary
tract infections