Diabetes mellitus

Continued……
1. Emergencies
2. Complications
3. Treatment
Diabetic Emergencies
Hyperglycemic
HHNC: Hyperosmolar
Hyperglycemic
Nonketotic Coma
DKA: Diabetic
Ketoacidosis
Hypoglycemic
Diabetic Coma or
Insulin Reaction
HHS: Hyperglycemic Hyperosmolar State
 Effects Type 2 Diabetics
 Prominent later in life
 Elevated Blood Glucose leads to increase in serum osmolarity
 This results in Diuresis and Fluid Shift.
 Increased Urination causes body wide depletion of Water and
Electrolytes.
 Extreme Dehydration
 Physical Signs Symptoms
Tachycardia Nausea/vomiting
Orthostatic Vitals Abdominal pain
Poor Skin Turgor Polydipsia
Drowsiness and Polyuria
lethargy
Delirium
Coma
Treatment
IV FLUIDS !!!!!
Bolus of Normal Saline/ half normal saline will help to reverse
the overwhelming dehydration

Insulin?
NEXT
DKA: Diabetic Ketoacidosis
Dereased Insulin or Insulin resistance leads to Elevated
Blood Glucose levels

However, Cellular Glucose is Low without insulin

Equivalent to Starvation

As a result the body attempts to Compensate

Uses Glucose stores
Breaks Down Fat and Protein
In an attempt to save the Heart and Brain, the body
produces Ketone Bodies from fatty acids

Acetoacetate,
Beta-hydroxybutyrate,
Acetone

Excessive Ketones lead to Acidosis

Beta-hydroxybutyrate is a carboxylic Acid
Physical Signs Symptoms
Altered mental status Often insidious
Tachycardia Fatigue and malaise
Tachypnea or Nausea/vomiting
hyperventilation Abdominal pain
(Kussmaul respirations) Polydipsia
Normal or low blood Polyuria
pressure Polyphagia
Lethargy and weakness Weight loss
Fever Fever
Acetone odor of the breath
reflecting metabolic
acidosis
Treatment
Fluids!!!!!
It is important to initiate Fluid Ressusitation
Begin With Normal Saline
Insulin
This Will Start in the Emergency Dept.
Hypoglycemia
Treatment
Patient’s will present with Altered Mental Status
Supplemental Oxygen
Vitals
IV Fluids Monitor
Glucometry
Glucose < 80 mg/dL, Considered Hypoglycemia
Treatment
Glucose Supplementation
Oral Glucose
Juice, Non- Diet Soda
Oral Glucose Solution
D10
250cc Bolus
D50
25 gram glucose in 50ml water, IV
Glucagon
Naturally Occurring Hormone, From Pancreas Alpha-Cells
Breaks Down Stored Glycogen to Glucose
1U = 1mg Given IM/SC
Pediatric 0.025 mg/kg IM/SC to max dose 1mg
Blood Glucometry
Measurement of Blood
Glucose levels
Hospital labs evaluate
Serum Glucose (10-15%
higher)
Requires a small
sample of blood
No IV’s or Phlebotomy
Only seconds to obtain
results
Glucometry Technique
1. Wash hands with soap and warm water and dry
completely or clean the area with alcohol and dry
completely.
2. Prick the fingertip with a lancet.
3. Hold the hand down and hold the finger until a small
drop of blood appears; catch the blood with the test
strip.
4. Follow the instructions for inserting the test strip and
using the SMBG meter.
5. Record the test result.
CHRONIC COMPLICATIONS IN
DIABETES MELLITUS
MAJOR DETERMINING FACTORS

Duration

Glycemic Control ( Hb A 1 C)

Type 1 vs. Type 2

Macrovascular Damage Affects Large (Named) Arteries:

Coronary Arteries

Coronary artery disease

MI

Carotid/Cerebral Arteries

Stroke

TIA

Lower Extremity Arteries

Peripheral vascular disease

Microvascular Damage Affects:

Retinas

proliferative and non proliferative

blindness

Glomeruli

diabetic nephropathy

Nerves

diabetic neuropathy small fibre/ large fibre

Microvascular Damage Causes:

Blindness

End-Stage Renal Disease

Neuropathy >>> Amputations

The Role of Insulin
High insulin levels as seen in insulin resistance
MAY be contributory to the development of:
Hypertension
Atherosclerosis
So HOW does diabetes damage blood vessels?

Best understood mechanism is by non-enzymatic

glucosylation (glycation) of proteins and other
macromolecules.

Other mechanisms postulated include changes in

NADP+ and NADH levels associated with alternative
glucose metabolic fates when usual pathways are
saturated.
Chronic hyperglycemia causes increased glycation of
proteins, resulting in Advanced Glycation
Endproducts (AGEs)

These can cause damage through loss of function,

turning on/off signal pathways within cells, or
alteration in gene expression.
One of the proteins which is glycated is Hemoglobin.
Because it is found in the blood, it is convenient to
measure as HbA1c.

Because RBCs (and thus Hb) survive in the blood for 90-
120 days, the HbA1c provides a means to assess
glycemic control over this period.
Insulin therapy
who needs
what are the types
How to administer
 Insulin is a small protein consisting of an A
A chain chain of 21 amino acids linked by two disulfide
(S—S) bridges to a B chain of 30 amino acids.

Beta cells have channels in their plasma

membrane that serve as glucose
detectors. Beta cells secrete insulin in
response to a rising level of circulating
glucose.
B chain
Who need insulin medicine
 Type I (insulin dependent) diabetes patients whose body
produces no insulin.
 Type 2 diabetes patients that do not always produce enough
insulin.
Insulin drug evolution
Stage 1 Insulin was extracted from the glands of cows
and pigs. (1920s)

Stage 2 Convert pig insulin into human insulin by

removing the one amino acid that distinguishes them
and replacing it with the human version.
 Stage 3 Insert the human
insulin gene into E. coli and
culture the recombinant E.coli
to produce insulin (trade name
= Humulin®). Yeast is also
used to produce insulin (trade
name =
Novolin®) (1987).

Recombinant DNA technology has also made it possible to manufacture

slightly-modified forms of human insulin that work faster (Humalog® and
NovoLog®) or slower (Lantus®) than regular human insulin.
Types of insulin

Regular insulins

Insulin analogs

Pre-mixed insulin

Short peptide mimics

Regular insulins:

Human insulin: Humulin® (from E.coli),

Novalin® (from yeast)
NPH - neutral protamine Hagedorn (NPH),
protamine mixed.
Lente® insulin / Ultralente® insullin-
zinc added
Atrapid
yellow
short acting
Peak 2- 4 hrs
Total duration of action 6 hrs

Insulatard
green
intermediate acting
Peak 4- 6 hrs
Total duration of action 8 – 10 hrs
Split and mixed dose How to monitor
Total insulin need Morning atrapid – prelunch
FBS – 50 Morning insulatard
10 6 pm RBS
= total requirement
2/3 rd as insulatard Evening atrapid – bed time
1/3 rd as atrapid Night insulatard
FBS
2/3 rd in morning
1/3 rd at night
How to administer insulin Every area has different
1.Subcutaneous amount of blood supply
2.Never mix NPH/ glargine and absorption varies
with other insulin
3.Rotate sites Change sites once in ten to
4.Deltoid, abdomen, thigh fourteen days

Chronic insulin therapy may

lead to lipodystrophy
Insulin Analogs:

 Fatty Acid Acylated insulins

 Insulin Lispro (Humalog®) (1996)

 Insulin Aspart (NovoLog®) (2000)

 Insulin Glargine (Lantus®) (2002)

 Insulin Detemir (Levemir®) (Jun.,2005)

 Insulin Glulisine (Apidra®) (Jan., 2006)

Diabetes – Oral Medications

Sulfonylureas
Biguanides
Thiazolidinediones
Alpha-glycosidase inhibitors
Meglitinides
Sulfonylureas : stimulate β cells to produce more insulin
1st generation
tolbutamide
tolazamide
Chlorpropamide

2nd generation
glipizide
Glyburide
micronized
 glyburide

3rd generation
glimepiride
Sulfonylureas interact with receptors on pancreatic b-
cells to block ATP-sensitive potassium channels

This, in turn, leads to opening of calcium channels

Which leads to the production of insulin
Biguanides : improves insulin’s ability to move
glucose into cells (esp. muscle)

Metformin

- Metformin was first described in the scientific

literature in 1957 (Unger et al).
- It was first marketed in France in 1979 but did not
receive FDA approval for Type 2 diabetes until 1994.

Metformin is a widely used monotherapy, and also

used in combination with the sulfonylureas in
treatment of type 2 diabetes
Thiazolidinediones (TZD’s) : make cells more sensitive to
insulin (esp. fatty cells)

Pioglitazone
Rosiglitazone

-PPARγ is a member of the steroid hormone nuclear receptor

superfamily,

- and is found in adipose tissue, cardiac and skeletal muscle, liver and
placenta
TZD s binds to and activates the gamma isoform of
the

- peroxisome proliferator-activated receptor

(PPARγ). PPAR - γ
 Thiazolidinediones

PPAR

Insulin Insulin and sdLDL Other vascular Anti-inflammatory

Glucose
resistance proinsulin effects effects
HDL2 HDL2
CRP, IL-6
ACR
ROS, MCP-1
MMP-9 P47phox
PAI-1 TNFα
Vasc react.

? Cardiovascular implications
 Block enzymes that help digest starches 

slowing the rise in blood glucose.

Polysacchride to monosachhride conversion is blocked

Better for post prandial glucose control

One with each meal

S/E flatulence
AGI’s
- Precose ® (acarbose),

- Glyset ® (miglitol)
Meglitinides : Stimulate more insulin production ;
dependant upon level of glucose present

Repaglinide

Nateglinide
 Diabetes – Oral Medications
Summary

Sulfonylureas stimulate β cells

Biguanides improves insulin’s ability to move glucose
Thiazolidinediones cells more sensitive to insulin
Alpha-glycosidase inhibitors Block enzymes that help
digest starches
Meglitinides stimulate β cells (dependant upon glucose
conc.)
 To conclude….

2 major types of diabetes

(3 with Gestational)
 Type 1 => insulin dependant (5-10%)
 Type 2 => may treat with oral medication which may
alter insulin production &/or sensitivity ; disease often
succumbs to insulin dependence (>90%)
Diabetes is a leading cause of blindness, kidney failure,
amputation, heart attack, stroke, and premature death.

Target FBS 90 – 130 mg/dL

HbA1C < 7

These complications can be minimized!

 Early Diagnosis of DM
 Monitoring for complication
 Aggressive treatment of co-risk factors
 Team approach - access to multiple specialists