Diabetes and Diabetic DKa

1. Diabetes mellitus
(DM) & DKa
Stephen Satyanand Ram
July 22nd 2016
Dr. C Bowman

2. Diabetes mellitus (DM)
• commonly referred to as diabetes(sugar)
• is a group of metabolic diseases in which there are high
blood sugar levels over a prolonged period
• is due to either the pancreas not producing
enough insulin (insulin deficiency)
• or the cells of the body not responding properly to the
insulin produced. (insulin resistance)

3. Epidemiology
• As of 2013, 382 million people have diabetes world wide.Type 2 makes up
about 90% of the cases. This is equal to 8.3% of the adult population with
equal rates in both women and men.
• Diabetes mellitus occurs throughout the world but is more common
(especially type 2) in more developed countries. The greatest increase in
rates was expected to occur in Asia and Africa, where most people with
diabetes will probably live in 2030.The increase in rates in developing
countries follows the trend of urbanization and lifestyle changes, including
a "Western-style" diet.

4. Rates of Diabetes
worldwide

5. Main Types of DM
• Type 1 DM : results from the pancreas's failure to produce enough insulin.
This form was previously referred to as "insulin-dependent diabetes
mellitus" (IDDM) or "juvenile diabetes".
• Type 2 DM: begins with insulin resistance, a condition in which cells fail to
respond to insulin properly. As the disease progresses a lack of insulin may
also develop. The primary cause is excessive body weight and due to
sedentary life style.
• Gestational diabetes: is the third main form and occurs when pregnant
women without a previous history of diabetes develop high blood-sugar
levels.

6. Type 1
• Type 1 diabetes mellitus is characterized by loss of the insulin-
producing beta cells of the islets of Langerhans in the pancreas, leading
to insulin deficiency.
• This type can be further classified as immune-mediated or idiopathic. The
majority of type 1 diabetes is of the immune-mediated nature, in which
a T-cell-mediated autoimmune attack leads to the loss of beta cells and
thus insulin.
• It causes approximately 10% of diabetes mellitus cases in North America
and Europe. Most affected people are otherwise healthy and of a healthy
weight when onset occurs. Sensitivity and responsiveness to insulin are
usually normal, especially in the early stages

7. • "Brittle" diabetes, also known as unstable diabetes or labile diabetes, is
a term that was traditionally used to describe the dramatic and recurrent
swings in glucose levels, often occurring for no apparent reason
in insulin-dependent diabetes. This term, however, has no biologic basis
and should not be used. Still, type 1 diabetes can be accompanied by
irregular and unpredictable high blood sugar levels, frequently
with ketosis, and sometimes with serious low blood sugar levels. Other
complications include an impaired counter regulatory response to low
blood sugar, infection, gastroparesis (which leads to erratic absorption
of dietary carbohydrates), and endocrinopathies (e.g., Addison's
disease). These phenomena are believed to occur no more frequently
than in 1% to 2% of persons with type 1 diabetes.

8. Type 2 DM is the most common type of diabetes mellitus.
In the early stage of type 2, the predominant abnormality is
reduced insulin sensitivity. At this stage, high blood sugar can be
reversed by a variety of measures and medications that improve
insulin sensitivity or reduce the liver's glucose production.
Type 2 DM is due primarily to lifestyle factors and genetics] A
number of lifestyle factors are known to be important to the
development of type 2 DM, including obesity (defined by a bod
mass index of greater than 30), lack of physical activity, poor diet,
stress, and urbanization. Excess body fat is associated with 30%
of cases in those of Chinese and Japanese descent, 60–80% of
cases in those of European and African descent, and 100% of
Pima Indians and Pacific Islanders. Even those who are not obese
often have a high waist–hip ratio.
Type 2

9. Comparison of type 1 and 2 DM

10. Gestational diabetes
• Gestational diabetes mellitus (GDM) resembles type 2 DM in
several respects, involving a combination of relatively inadequate
insulin secretion and responsiveness.
• It occurs in about 2–10% of all preganacies and may improve or
disappear after delivery.
• However, after pregnancy approximately 5–10% of women with
gestational diabetes are found to have diabetes mellitus, most
commonly type 2.
• Gestational diabetes is fully treatable, but requires careful
medical supervision throughout the pregnancy. Management
may include dietary changes, blood glucose monitoring, and in
some cases, insulin may be required.

11. Risk to the unborn fetus in GDM
• untreated gestational diabetes can damage the health of the fetus or
mother. Risks to the baby include macrosomia (high birth weight),
congenital heart and central nervous system abnormalities, and skeletal
muscle malformations.
• Increased levels of insulin in a fetus's blood may inhibit
fetal surfactant production and cause respiratory distress syndrome. A high
blood bilirubin level may result from red blood cell destruction.
• In severe cases, perinatal death may occur, most commonly as a result of
poor placental perfusion due to vascular impairment. Labor induction may
be indicated with decreased placental function.
• A Caesarean section may be performed if there is marked fetal distress or
an increased risk of injury associated with macrosomia, such as shoulder
dystocia

12. Sings and symptoms
Individuals can experience different signs and symptoms
of diabetes, and sometimes there may be no signs. Some
of the signs commonly experienced include:
•Frequent urination (polyuria)
•Excessive thirst (polydipsia)
•Increased hunger (polyphagia)
•Weight loss
•Itchy skin (pruritus)
•Fatigue
•A tingling sensation or numbness in the hands or feet
•Blurred vision
•Frequent infections
•Slow-healing wounds

13. • Insulin is the principal hormone that regulates the uptake of glucose from
the blood into most cells of the body, especially liver, muscle, and
adipose tissue.
• Therefore, deficiency of insulin or the insensitivity of its receptors plays a
central role in all forms of diabetes mellitus.
• The body obtains glucose from three main places: the intestinal
absorption of food, the breakdown of glycogen, the storage form of
glucose found in the liver, and gluconeogenesis, the generation of
glucose from non-carbohydrate substrates in the body.
Pathophysiology

14. Diagnosis
characterized by recurrent or persistent high blood sugar, and is diagnosed by
demonstrating any one of the following
• Fasting plasma glucose level
≥ 7.0 mmol/l (126 mg/dl)
• Plasma glucose ≥ 11.1 mmol/l
(200 mg/dl) two hours after a 75 g
oral glucose load as in a glucose
tolerance test
• Symptoms of high blood sugar
and casual plasma glucose
≥ 11.1 mmol/l (200 mg/dl)
• Glycated hemoglobin (HbA1C)
≥ 48 mmol/mol (≥ 6.5 DCCT %)

15. Management
Management concentrates on keeping blood sugar levels as close to normal, without
causing low blood sugar. This can usually be accomplished with a healthy diet,
exercise, weight loss, and use of appropriate medications (insulin in the case of type 1
diabetes; oral medications, as well as possibly insulin, in type 2 diabetes).
-Medications
-Dietary and exercise modification
-Regular complication monitoring
-Self monitoring of blood glucose
-Control of BP and lipid level

16. Treatment
Pharmacological therapy
-Insulin (Type 1 and Type 2 DM)
-Sulfonylurea (Type 2 DM)
-Biguanides (Type 2 DM)
-Meglitinides (Type 2 DM)
-Thiazolidinediones Glitazones (Type
2 DM)
-a-Glucosidase inhibitors (Type 2
DM)

17. Insulin
Strength
-The number of units/ml
e.g. U-100 , U-20, U-10
Source
-Pork:
-Human (recombinant DNA
technology)

18. Onset and duration of effect
Changing the properties of insulin preparation can alter
the onset and duration of action
-Lispro: (Monomeric) absorbed to the circulation very
rapidly
-Aspart:(Mono- and dimeric) absorbed to the circulation
very rapidly
-Regular: (Hexameric) absorbed rapidly but slower
than lispro and aspart

19. Rapid-acting insulin
e.g. Insulin lispro and insulin aspart
Short-acting insulin
e.g. Regular insulin
Intermediate-acting insulin
e.g. NPH and Lente insulin
Long-acting insulin
e.g. Insulin Glargine

20. How much insulin ?
-A good starting dose is 0.6 U/kg/day
-The total dose should be divided to:
-45% for basal insulin
-55% for prandial insulin
The prandial dose is divided to
-25% pre-breakfast
- 15% pre-lunch
- 15% pre-supper

21. Example: For a 50 kg patient
-The total dose = 0.6X50 = 30 U/day
-13.5 U for basal insulin (45% of dose)
-Administered in one or two doses
-16.5 U for prandial insulin (55% of dose)
The 16.5 U are divided to:
-7.5 U pre-breakfast (25%)
- 4.5 U pre-lunch (15%)
- 4.5 U pre-supper (15%)

22. Sulfonylureas
Stimulate the pancreatic secretion of insulin
Classification:
First generation
•e.g. tolbutamide, chlorpropamide, and acetohexamide
•Lower potency, more potential for drug interactions and side effects
Second generation
•e.g. glimepiride, glipizide, and glyburide
•higher potency, less potential for drug interactions and side effects
All sulfonylurea drugs are equally effective in reducing the blood glucose
when given in equipotent doses

23. Biguanides Metformin
(Glucophage)
Pharmacological effect
–Reduces hepatic glucose production
–Increases peripheral glucose utilization
Adverse effects
–Nausea, vomiting, diarrhea, and anorexia
–As a precaution metformin should not be used
in patients with renal insufficiency, CHF,
conditions that lead to hypoxia

24. pancreas transplant is occasionally considered for people with type 1 diabetes
who have severe complications of their disease, including end stage kidney
disease requiring kidney transplantation.
Weight loss surgery in those with obesity and type two diabetes is often an
effective measure. Many are able to maintain normal blood sugar levels with
little or no medications following surgery and long-term mortality is decreased.
There however is some short-term mortality risk of less than 1% from the
surgery. The body mass index cutoffs for when surgery is appropriate are not
yet clear. It is recommended that this option be considered in those who are
unable to get both their weight and blood sugar under control.
Surgery

25. Complications
• The major long-term complications relate to damage to blood vessels. Diabetes
doubles the risk of cardiovascular disease and about 75% of deaths in
diabetics are due to coronary artery disease.
• Other "macrovascular" diseases are stroke, and peripheral vascular disease.
• The primary complications of diabetes due to damage in small blood vessels
include damage to the eyes, kidneys, and nerves.
• Damage to the eyes, known as diabetic retinopathy, is caused by damage to
the blood vessels in the retina of the eye, and can result in gradual vision loss
and blindness.
• Damage to the kidneys, known as diabetic nephropathy, can lead to tissue
scarring, urine protein loss, and eventually chronic kidney disease, sometimes
requiring dialysis or kidney transplant.
• Damage to the nerves of the body, known as diabetic neuropathy,

26. DKA (Ketoacidosis) & Ketones
DKA (Ketoacidosis) & Ketones
Diabetic ketoacidosis (DKA) is a serious condition that can lead to diabetic coma (passing out
for a long time) or even death. Is a complex metabolic state of hyperglycemia, ketosis, and
acidosis. Diabetic ketoacidosis results from untreated absolute or relative deficiency of insulin
in type 1 or type 2 diabetes mellitus, respectively.
• When your cells don't get the glucose they need for energy, your body begins to burn fat for energy,
which produces ketones.
• Ketones are chemicals that the body creates when it breaks down fat to use for energy. The body
does this when it doesn’t have enough insulin to use glucose, the body’s normal source of energy.
• When ketones build up in the blood, they make it more acidic. They are a warning sign that your
diabetes is out of control or that you are getting sick.

27. What are the Warning Signs of DKA?
Early symptoms include the following:
•Thirst or a very dry mouth
•Frequent urination
•High blood glucose (blood sugar) levels
•High levels of ketones in the urine
Then, other symptoms appear:
•Constantly feeling tired
•Dry or flushed skin
•Nausea, vomiting, or abdominal pain
Difficulty breathing
•Fruity odor on breath
•confusion

28. Laboratory tests
• Serum glucose level:
Serum glucose (eg, Accu-Chek, Dextrostix) determination of hyperglycemia provides
the opportunity for rapid diagnosis and treatment of diabetic ketoacidosis (DKA).
However, a urine analysis (dip for sugar and ketones) is also acceptable.
• Serum potassium level:
This is the most important electrolyte disturbance in patients with severe diabetic
ketoacidosis.
• Glycosylated hemoglobin:
In a patient with known diabetes, high percentages of glycosylated hemoglobin (Hgb
A1C) indicate poor compliance with insulin therapy.

29. • CBC count
Note that an increased WBC count may be a response to stress in diabetic
ketoacidosis and not necessarily a sign of infection.
• Other studies
include the following:
• Obtain serum sodium, chloride, bicarbonate, BUN, creatinine, magnesium,
calcium, and phosphate levels
• Urine glucose, ketones, and osmolality
• Serum osmolality
• Blood, urine, and throat cultures

30. Pathophysiology
• Hyperglycemia results from impaired glucose uptake because of insulin
deficiency and excess glucagon with resultant gluconeogenesis and
glycogenolysis.
• Glucagon excess also increases lipolysis with the formation of ketoacids. Ketone
bodies provide alternative usable energy sources in the absence of intracellular
glucose.
• The ketoacids (acetoacetate, beta-hydroxybutyrate, acetone) are products of
proteolysis and lipolysis.
• Hyperglycemia causes an osmotic diuresis that leads to excessive loss of free
water and electrolytes. Resultant hypovolemia leads to tissue hypoperfusion
and lactic acidosis.

31. • Ketosis and lactic acidosis produce a metabolic acidosis; however,
supplemental bicarbonate is not recommended.
• Acidosis usually resolves with isotonic fluid volume replenishment and
insulin therapy. A pediatric trial of bicarbonate in severe metabolic
acidosis during DKA (pH < 7.15) showed no benefit when compared with
placebo.
• Indeed, multiple studies suggest that bicarbonate therapy may cause
paradoxical intracellular acidosis, worsening tissue perfusion
and hypokalemia, and cerebral edema.

32. Management
With current medical therapy, diabetic ketoacidosis has a 2-5% mortality
rate. Mortality results from the precipitating underlying cause, which is
primarily cerebral edema. Cerebral edema occurs in 0.3-1% of all
episodes of diabetic ketoacidosis.
• Provide oxygen and advanced airway management in patients with
diabetic ketoacidosis (DKA), if needed.
• Monitor the patient.
• Provide isotonic intravenous fluids (eg, isotonic sodium chloride
solution or lactated Ringer solution).
• Electrolyte replacement.

33. References
 Kisiel M, Marsons L. Recognizing and responding to hyperglycaemic emergencies. Br J
Nurs. 2009 Oct 8-21. 18(18):1094-8. [Medline].
 Kurien M, Mollazadegan K, Sanders DS, Ludvigsson JF. A nationwide population-based
study on the risk of coma, ketoacidosis and hypoglycemia in patients with celiac disease
and type 1 diabetes. Acta Diabetol. 2015 Sep 24. [Medline].
 Hsia DS, Tarai SG, Alimi A, Coss-Bu JA, Haymond MW. Fluid management in pediatric
patients with DKA and rates of suspected clinical cerebral edema. Pediatr Diabetes.
2015 Aug. 16 (5):338-44. [Medline].
 Wolfsdorf J, Glaser N, Sperling MA; American Diabetes Association. Diabetic
ketoacidosis in infants, children, and adolescents: A consensus statement from the
American Diabetes Association. Diabetes Care. 2006 May. 29(5):1150-9. [Medline].