Complication of diabetes

2. •Definition
•Etiology
•Pathogenesis
•Clinical Features
•Investigation
•Management
•Complication
•Prevention

3. DKA is a syndrome in which insulin deficiency and glucagon
excess combine to produce a hyperglycemic, dehydrated, acidotic
patient, with profound electrolyte imbalance.
The cardinal biochemical features are:
• Hyperketonaemia (≥ 3 mmol/L) and ketonuria (more than 2+ on
standard urine sticks)
• Hyperglycaemia (serum glucose > 13.9 mmol/L [250 mg/dL]
• Metabolic acidosis (venous bicarbonate < 15 mmol/L and/or
venous pH < 7.3).

4. Etiology
It is due to the insulin deficiency occurring as a result of either
inadequate administration of exogenous insulin or a stressful
condition.
Stresses can be:
1. Infection (pneumonia, UTI, URI, meningitis, cholecystitis or
pancreatitis)
2. Vascular disorder (MI, CVD)
3. Endocrine disorder (hyperthyroidism, Cushing’s syndrome,
acromegaly, pheochromocytoma)
4. Trauma
5. Pregnancy
6. Emotional stress (especially in adolescence).
7. Drugs—cocaine.

5. Pathogenesis
•The decreased ratio of insulin to glucagon promotes
gluconeogenesis, glycogenolysis, and ketone body formation in the
liver, as well as increases in substrate delivery from fat and muscle
(free fatty acids, amino acids) to the liver.
•Ketoacidosis is a state of uncontrolled catabolism associated with
insulin deficiency(stimulate lipoprotein lipase which break down
fat store into free fatty acid)
•In the absence of insulin there is an unrestrained increase in hepatic
gluconeogenesis
• High circulating glucose levels result in an osmotic diuresis by the
kidneys and consequent dehydration.
• In addition, peripheral lipolysis leads to an increase in circulating
free fatty acids, which are converted within the liver to acidic
ketones, leading to a metabolic acidosis.
•These processes are accelerated by the ‘stress hormones’ –
catecholamines, glucagon and cortisol – which are secreted in
response to dehydration and intercurrent illness

6. •The combination of insulin deficiency and hyperglycemia
reduces the hepatic level of fructose-2,6-bisphosphate, which
alters the activity of phosphofructokinase and fructose-1,6-
bisphosphatase.
•Glucagon excess decreases the activity of pyruvate kinase,
whereas insulin deficiency increases the activity of
phosphoenolpyruvate carboxykinase. These changes shift the
handling of pyruvate toward glucose synthesis and away from
glycolysis.
•The increased levels of glucagon and catecholamines in the face
of low insulin levels promote glycogenolysis.
•Insulin deficiency also reduces levels of the GLUT4 glucose
transporter, which impairs glucose uptake into skeletal muscle
and fat and reduces intracellular glucose metabolism

8. Symptoms
• Polyuria, thirst
• Weight loss
• Weakness
• Nausea, vomiting
• Leg cramps
• Blurred vision
• Abdominal pain
Signs
• Dehydration
• Hypotension (postural or supine)
• Cold extremities/peripheral cyanosis
• Tachycardia
• Air hunger (Kussmaul breathing)
• Smellof acetone
• Hypothermia
• Confusion, drowsiness, coma (10%)
Kussmaul respirations and a fruity odor on the patient’s breath (secondary to
metabolic acidosis and increased acetone) are classic signs of the disorder

9. Investigations
The following are important but should not delay the institution of
intravenous fluid and insulin replacement:
• Venous blood:
Serum electrolytes (K+, Na+, Mg2+, Cl–, bicarbonate,
phosphate)
Acid-base status—pH, HCO3–, Pco2, β-hydroxybutyrate
Renal function (creatinine, urine output
• Urine or blood analysis for ketones
• ECG.
• Infection screen: full blood count, blood and urine culture, C-
reactive protein, chest X-ray. Although leucocytosis invariably
occurs in DKA, this represents a stress response and does not
necessarily indicate infection.
Serum or plasma assays for β-hydroxybutyrate are preferred because they more accurately
reflect the true ketone body level as β-hydroxybutyrate, is synthesized at a threefold
greater rate than acetoacetate.

10. Management
•The aims of treatment are to replace fluid and electrolyte loss, replace insulin,
and restore acid–base balance over a period of about 24 hours
• After initiating IV fluid replacement and insulin therapy, the agent or event that
precipitated the episode of DKA should be sought and aggressively treated.
• If the patient is vomiting or has altered mental status, a nasogastric tube should
be inserted to prevent aspiration of gastric contents
1. Confirm diagnosis (↑ plasma glucose, positive serum ketones, metabolic
acidosis).
2. Admit to hospital; intensive care setting may be necessary for frequent
monitoring or if pH <7.00 or unconscious.
3. Assess: Serum electrolytes (K+, Na+, Mg2+, Cl–, bicarbonate, phosphate)
Acid-base status—pH, HCO3–, Pco2, β-hydroxybutyrate
Renal function (creatinine, urine output)

11. 4. Replace fluids:
• 2–3 L of 0.9% saline over first 1–3 h (10–20 mL/kg per hour);
subsequently, 0.45% saline at 250–500 mL/h; When
hemodynamic stability and adequate urine output are
achieved, IV fluids should be switched to 0.45% saline
depending on the calculated volume deficit.
• Change to 5% glucose and 0.45% saline at 150–250 mL/h
when plasma glucose reaches 250 mg/dL (13.9 mmol/L).
• Be more cautious with fluid replacement in elderly, young
people, pregnant patients and those with renal or heart
failure. If plasma sodium is > 155mmol/L, 0.45% sodium
chloride may be used.

12. 5. Administer short-acting regular insulin:
• IV (0.1 units/kg), then 0.1 units/kg per hour by continuous IV
infusion; increase two- to threefold if no response by 2–4 h.
• If the initial serum potassium is <3.3 mmol/L (3.3 meq/L), do not
administer insulin until the potassium is corrected
• IV administration is usually preferred (0.1 units/kg of regular
insulin per hour) because it ensures rapid distribution and
allows adjustment of the infusion rate as the patient responds
to therapy
• IV regular insulin should be continued until the acidosis resolves
and the patient is metabolically stable. As the acidosis and
insulin resistance associated with DKA resolve, the insulin
infusion rate can be decreased (to 0.02–0.1 units/kg per hour).
• Long-acting insulin, in combination with SC short-acting insulin,
should be administered as soon as the patient resumes eating.

13. 6. Assess patient: What precipitated the episode (noncompliance,
infection, trauma, pregnancy, infarction, cocaine)? Initiate
appropriate workup for precipitating event (cultures, CXR, ECG).
7. Measure capillary glucose every 1–2 h; measure electrolytes
(especially K+, bicarbonate, phosphate) and anion gap every 4 h for
first 24 h.
8. Monitor blood pressure, pulse, respirations, mental status, fluid
intake and output every 1–4 h.
9. Replace K+:
• 10 meq/h when plasma K+ <5.0–5.2 meq/L (or 20–30 meq/L of
infusion fluid), ECG normal, urine flow and normal creatinine
documented;
• 40–80 meq/h when plasma K+ <3.5 meq/L or if bicarbonate is
given.
• If initial serum potassium is >5.2 mmol/L (5.2 meq/L), do not
supplement K+ until the potassium is corrected.

14. 10. Despite a bicarbonate deficit, bicarbonate replacement is not usually necessary,
bicarbonate administration and rapid reversal of acidosis may impair cardiac
function, reduce tissue oxygenation, and promote hypokalemia.
However, in the presence of severe acidosis (arterial pH <7.0), the ADA advises
bicarbonate (50 mmol [meq/L] of sodium bicarbonate in 200 mL of sterile water
with 10 meq/L KCl per hour for 2 h until the pH is >7.0).
11. Hypophosphatemia may result from increased glucose usage, but randomized
clinical trials have not demonstrated that phosphate replacement is beneficial in
DKA.
If the serum phosphate is <0.32 mmol/L (1 mg/dL), then phosphate supplement
should be considered and the serum calcium monitored.
12. Hypomagnesemia may develop during DKA therapy and may also require
supplementation
13. Continue above until patient is stable, glucose goal is 8.3–11.1 mmol/L (150–200
mg/dL), and acidosis is resolved. Insulin infusion may be decreased to 0.02–0.1
units/kg per hour.
14. Administer long-acting insulin as soon as patient is eating. Allow for a 2–4 hour
overlap in insulin infusion and SC long-acting insulin injection

15. Additional procedures
• Catheterisation if no urine passed after 3hrs
• Central venous lineif cardiovascular system compromised, to allow
fluid replacement to be adjusted accurately – also consider in
elderly, pregnant, renal or cardiac failure, other serious
comorbidities, severe DKA
• Measure arterial blood gases and repeat chest X-ray if O2
saturation <92%
• ECG monitoring in severe cases
• Thromboprophylaxis with low molecular weight heparin

16. Complication
•Cerebral edema
•Venous thrombosis
•Upper GI bleeding
•Acute respiratory distress syndrome
•Death

17. Prevention
• Frequently measure the capillary blood glucose;
• Measure urinary ketones when the serum glucose 16.5
mmol/L(300mg/ dL);
• Drink fluids to maintain hydration;
• Continue or increase insulin;
• Seek medical attention if dehydration, persistent vomiting, or
uncontrolled hyperglycemia develop.
• Using these strategies, early DKA can be prevented or detected
and treated appropriately on an outpatient basis.

18. Hyperglycemic Hyperosmolar state

19. Reference
•Harrison Principles of Internal Medicine
•Davidson’s Principles & Practice of Medicine
•Essentials of Kumar & Clark’s Clinical Medicine
•Rosen’s Emergency Medicine