Complications of diabetes

Question 1

Acute complications

Answer 1

-Diabetic ketoacidosis
-Hyperosmolar hyperglycemic state
-hypoglycemia
-lactic acidosis

Question 2

DKA occurs more in

Answer 2

Type 1 diabetes

Question 3

Pathogenesis of DKA

Answer 3

Uncontrolled catabolism associated with marked insulin deficiency and elevated counter-regulatory hormones, which accelerated the effects of insulin deficiency.
Hyperglycemia causes osmotic diuresis leading to dehydration and loss of electrolytes.
Uncontrolled lipolysis in adipose tissue and uncontrolled ketogenesis in the liver. Insulin inhibits hepatic ketogenesis and the breakdown of adipose triglycerides to non-esterified fatty acids (NEFAs). NEFAs are transported to the liver where the absence of insulin impairs the hepatic re-esterification of NEFA to triglycerides, so they are oxidized into acidic ketone bodies.
The liver exports the ketone bodies where they build up due to the impaired uptake to peripheral tissue (eg muscle).

Question 4

Ketone bodies

Answer 4

Acetoacetic acid
3-hydroxybutyric acid
Acetone

Question 5

Clinical features of DKA

Answer 5

-Acetone breath
-severe metabolic acidosis
-vomiting (ketone bodies are nauseating)
-hyperventilation, ‘air hunger’ (compensation for acidosis)
-prostration
-abdominal pain
-confusion
-coma

Question 6

Indicators of severe DKA

Answer 6

-blood ketones over 6 mmol/l
-bicarbonate below 5 mmol/l
-venous/arterial ph below 7
-hypokalemia on admission
-GCS < 12 or abnormal APVU scale
-oxygen saturation below 92% on air
-SBP < 90mmhg
-tachycardia or bradycardia
-anion gap above 16

Question 7

Diagnosis of DKA

Answer 7

-ketonaemia >=31mg/dL or significant ketonuria >=2 on standard urine sticks
-blood glucose > 11mmol/L or known diabetes mellites
-bicarbonate below 15 mmol/L and/or venous ph < 7.3

Question 8

Chronic complications of diabetes

Answer 8

Microvascular complications
Macrovascular complications

Question 9

Cardinal feature of microvascular complication

Answer 9

Thickening of the capillary and arteriole basement membrane

Question 10

Pathology of microvascular complication

Answer 10

-formation of advanced glucation end products (AGE)
-increased flux of glucose through the sorbitol-polyol pathway
-abnormal microvascular blood flow
-growth factors and cytokines
-growth hormone—insulin-like growth factor axis

Question 11

Formation of advanced glycation end products (AGE)

Answer 11

Glucose binds irreversibly to form AGE in presence of prolonged hyperglycemia. AGEs cause tissue injury and inflammation via stimulation of proinflammatory factors such as complement and cytokines

Question 12

Sorbitol-polyol pathway

Answer 12

During hyperglycemia, excess glucose is metabolized to sorbitol via the polyol pathway. This leads to accumulation of sorbitol and fructose, which causes changes in vascular permeability, cell proliferation and capillary structure via stimulation of protein kinase C and transforming growth factor-beta.

Question 13

Growth factors and cytokines

Answer 13

Through increased expression of protein kinase c beta, a number of mitogenic cytokines and growth factors, including TGF-beta, TNF, VEGF, are upregulated.

Question 14

Growth hormone—insulin-like growth factor axis

Answer 14

The reduction of portal insulin concentrations impairs the ability of growth hormone to generate IGF-I in the liver, which in turn leads to growth hormone hypersécrétion by the pituitary gland. Growth hormone has been implicated in the development of microvascular complications.

Question 15

Most commonly diagnosed diabetes-related complication?

Answer 15

Diabetic retinopathy