Diabetes Complications

Treatment

Hypoglycemia
Sweating, tremor, tachycardia, anxiety, hunger
MOA: dec. blood glucose (+) Epi
Post-prandial (low blood glucose after lunch
Fasting (improves w/ sugar)

Insulinoma Hyperinsulinism: benign insulin-producing

tumor
serum insulin 8 ug/mL & blood glucose <40 mg/dL
(inappropriate high insulin despite low blood glucose)
elevated plasma insulin and insulin:glucose
elevated proinsulin and C peptide

Factitious Hyperinsulinism: self-ingestion of insulin

Glucagon:
Use:
Hypoglycemia
Severe hypoglycemia (1mg IV)
Endocrine diagnosis
Beta-blocker OD (inc. cAMP in heart)
increased insulin release Hypoglycemia
Radiology of bowel (relaxes intestine)
Dextrose: Use: Hypoglycemia, DKA
Diazoxide: Toxicity: hyperglycemia, ketoacitosis
If patient is conscious (>60 BGL) oral
glucose
If patient is unconscious (<40 BGL)
Glucagon

(GLIPIZIDE)
Triad of Hypoglycemia + Antibodies + Suppressed
plasma C peptide
Surgery: remove insulinoma
elevated plasma insulin and insulin:glucose ratio
Diabetic Ketoacidosis DM type I
IV regular insulin
Inc. plasma glucose (400 mg/dL), H+, ketones, K+
IV fluids
Dec. HCO3, Intracellular K+
Dextrose
Precipitated by: insufficient insulin therapy, infection, Balance electrolytes, K+
emotional stress, excess alcohol use
Presents w/ fruity odor of acetone on breath
Hyperosmolar coma/ Hyperosmolar Hyperglycemic Non-Ketotic Syndrome (HHNS) DM type II
Precipitated by: infections, strokes, MI, elderly, DM
Diagnosis: blood glucose >1000 mg/dL, high serum osmolality, high BUN, no ketosis
Due to Decreased Insulin & Increased Glucagon
Glut 2 beta cell
Higher Km (lower affinity) allows the muscles to utilized glucose
first.
o Need high amount of glucose to stimulate
Glut 4 muscle cells
Lower Km (higher affinity) allows muscles to utilize any small
amount of glucose.

Glucose GLUT 2 enters beta cell glucose metabolism inside

cell inc. ATP closure of K+ channels inc. K+ inside cell
depolarization stimulation/ opening of Ca++ channels Ca++ into beta cell degranulation
release insulin into circulation
-

70%/30% NPH/regular insulin

50%/50% NPL/Lispro insulin
75%/25% NPL/Lispro insulin
70%/30% NPA/Aspart insulin
Note: insulin glargine and detemir must be given as
separate injections.

Insulin indications:
DM (1/2 & gestational) Drug of choice for
Gestational
DKA
Hyperglycemia / Non-Ketotic Coma
How do you give the insulin shot? If u want to give 30
units/ day you have
to give 2/3 of the daily dose in the morning and give the remaining 1/3 at
night. This is to avoid hypoglycemia which could be caused by inc. activity and food during the day
-

Drug used to treat

Type II DM Drugs:

1st gen.
Sulfonylurease
(not used
clinically due to
AE)
2 gen.
Sulfonylurease
nd

Toblutamide
Tolzamide
Chlorpropramide

Glipizide

Glyburide

Meglitinides
(may be taken
alone or w/
biguanides)
Insulin
sensitizers

Glimepiride
Repaglinide
Nateglinide (Dphenylalanine)
Biguanide:

Metformin
*Euglycemic Rx (does
not cause
hypoglycemia)
*No weight gain

Thiazolidinedion
es:

Pioglitazone
Rosiglitazone
(AKA GLITAZONES)

Alphaglucosidase
inhibitors

Acarbose
Miglitol

DPP-4
inhibitors

Sitagliptin
Saxagliptin

GLP-1 agonist

Exenatide (IV)
Liraglutide (IV)

Amylin
synthetic
analog

Pramlintide

(amylin made in
the beta cells &
tells us when we
are full)

Bile-acid
sequestrants

Colesevelam

SGLT inhibitors

Canagliflozin
Dapagliflozin
Empagliflozin

Short t1/2. Indicated w/ elderly and

renal dysfunction
Short t1/2
Long duration (60h)
AE: Disulfiram-like rxn; SIADH,
jaundice, leucopenia, &
thrombocytopenia
Short-acting
Safe w/ mild to mod. renal
dysfunction
Dec. dose in hepatic dysfunction
Long-acting
Safe w/ mild-mod. hepatic
dysfunction
Dec. dose in renal dysfunction
Long-acting, once/daily dose

MOA: Block K+ channels

beta cells cell
depolarization Ca+ influx
Insulin granule release
Use: Type 2 DM (need working
Beta cell)

Contraindication: hepatic &

renal insufficiency
AE: hypoglycemia w/ longacting drugs, weight gain,
rashes, hypersensitivity
Rx Interactions: inc.
hypoglycemia w/ Cimetidine,
Insulin, Salicylates,
Sulfonamides

MOA: Same as Sulfonylureas but mainly stimulates the first phase

of insulin secretion
Use: Post-prandial hyperglycemia in type 2 DM. Indicated in pt. w/ sulfur
allergy
Nateglinide: safe in renal insufficiency, lower risk of hypoglycemia
MOA: (+) AMPK (-) mitochondrial Glycerol-3-phosphate DH (-)
glucose output from liver
Use: dec. insulin resistance in obese type 2 diabetics
AE: anorexia, nausea, vomiting, diarrhea, lactic acidosis (anion gap),
vit. B12 deficiency
Contraindications: alcoholism, renal & hepatic disease, chronic
cardiopulmonary disease, radiographic contrast, acidosis
MOA: bind PPAR-gamma in nucleus dec. insulin resistance inc.
glucose uptake dec TG levels
AE: fluid retention, edema, inc. risk of HF (especially Rosiglitazone),
weight gain, dec. bone mineral density, bone fractures in women,
hepatodoxiticy
Rx interactions: dec. efficacy of OC b/c is metabolized by cyt p450
MOA: (-) -glucosidase in GIT dec. glucose absorption dec.
demand for insulin
Use: control post-prandial hyperglycemia
AE: GI discomfort, flatulence, diarrhea, hepatotoxicity
MOA: (-) DPP4 (-) GLP1 inactivation inc. GLP1 action inc.
glucose-mediated insulin secretion & dec. glucagon lvls
AE: naso-pharyngitis, upper respiratory infections, headaches,
hypoglycemia, acute pancreatitis, joint pain
MOA: (+) glucose-mediated insulin secretion suppresses postprandial
glucagon release delays gastric emptying dec. appetite
Use: adjunct therapy w/ metformin or SU
AE: nausea, hypoglycemia w/ SU, necrotizing & hemorrhagic pancreatitis
Contraindication: Gastroparesis
MOA: suppress glucagon release delays gastric emptying CNS
mediated anorectic effects
Use:
- Modulate postprandial glucose levels
- Pre-prandial use in pts w/ type 1 and type 2 DM
AE: hypoglycemia
MOA: dec. FXR activation dec. glucose absorption dec. HbA1c by
only 0.5% & LDL by 15%
AE: constipation, indigestion, flatulence
Contraindications: hyperTGmia, pancreatitis, esophageal, gastric,
duodenal disorders
MOA: (-) SGLT2 (-) glucose reabsorption
AE: hypotension, dehydration, genital mycotic infections
Contraindications: severe renal impairment