14 DIABETES MELLITUS

Question 1

Diabetes

Answer 1

Diabetes mellitus
   deficiency of insulin
   resistance to effects of insulin
   Diabetes insipidus
   deficiency of antidiuretic hormone

Question 2

Insulin

Answer 2

peptide hormone
51 amino acids
produced in ß-cells of the islets of Langerhans of pancreas; they also produce glucagon and pancreatic polypeptide
released into bloodstream
binds to cell membrane receptors of target cells
regulates glucose uptake and metabolism, and a whole host of other stuff

Question 3

Insulin

Answer 3

skeletal muscle cells and fat cells require insulin to absorb glucose; both types can accumulate large carbohydrate reserves

neurons and a variety of other cells do not require insulin to absorb glucose; they cannot accumulate significant carbohydrate reserves

Question 4

Actions of insulin

Answer 4

uptake of glucose by cells
uptake of amino acids by cells
increased glycogen synthesis
increased synthesis and esterification of fatty acids
decreased lipolysis, proteinolysis and gluconeogenesis

Question 5

Control of insulin release

Answer 5

mainly direct feedback
ß-cells absorb glucose via glucose transporter GLUT2
complex metabolic pathway releases pre-synthesised insulin
some autonomic control
also released by cholecystokinin derived from enteroendocrine cells of intestinal mucosa

Question 6

Acute consequences of insulin deficiency

Answer 6

hyperglycaemia
ketosis
acidosis
hyperosmolar state

Question 7

Chronic consequences of insulin deficiency

Answer 7

cardiovascular disease
nephropathy
neuropathy
retinopathy

Question 8

Types of diabetes mellitus

Answer 8

Type 1
Type 2
Gestational
- WHO classification

Secondary

Question 9

Diabetes mellitus type 1

Answer 9

autoimmune destruction of ß-cells
probably triggered by viral infection
Coxsackie or rubella viruses
susceptibility partly dependent on HLA gene subtypes (HLA-DR3/DR4)
classically starts in childhood, though adult onset not rare

Question 10

Diabetes mellitus type 2

Answer 10

former names 
   non insulin dependent diabetes mellitus (NIDDM)
   obesity related diabetes mellitus
   adult-onset diabetes mellitus
   etc, etc

Question 11

Diabetes mellitus type 2

Answer 11

pathophysiology complicated
peripheral insulin resistance
ß-cell response to glucose delayed or absent
insulin concentrations normal or high
strong association with lifestyle
up to 20% prevalence in the elderly in the USA

Question 12

Gestational diabetes

Answer 12

genetic predisposition
insulin resistance, probably triggered by hormonal changes of pregnancy
resolves with delivery

Question 13

Risk factors for gestational diabetes

Answer 13

maternal age
   family history of DM type 2 
   African or North American native
   previous gestational diabetes
   previous baby over 4Kg
   smoking

Question 14

Dangers of gestational diabetes

mother

Answer 14

greater risk of DM type 2 later in life
hypertension
pre-eclampsia or eclampsia
obstructed labour

Question 15

Dangers of gestational diabetes

child

Answer 15

risk of DM type 2 later in life
   risk of obesity later in life
   macrosomia
   neonatal hypoglycaemia
   neonatal jaundice
   respiratory distress syndrome

Question 16

Secondary diabetes mellitus

Answer 16

chronic pancreatitis 
   cystic fibrosis
   pancreatic surgery
   haemachromatosis
   endocrine disease
   eg Cushing’s syndrome
   drug therapy
   eg corticosteroids

Question 17

Diabetes mellitus type 1

Answer 17

classical symptoms
   polyuria
   polydipsia
   hunger
   weight loss
  can be seen in DM type 2, but often camouflaged by other symptoms

Question 18

Diabetes mellitus type 1

Answer 18

polyuria
it is normal for glucose to be secreted into the urine in the glomerulus
at normal concentrations, all of this glucose is resorbed in the proximal renal tubule
threshold for resorption is about 10mmol/l; higher concentrations lead to glycosuria
glycosuria leads to osmotic polyuria
polyuria leads to polydipsia

Question 19

Biochemical diagnosis of diabetes mellitus

Answer 19

criteria
fasting plasma glucose level at or above 7.0mmol/l
plasma glucose at or above 11.1mmol/l two hours after a 75g oral glucose load
random plasma glucose at or above 11.1mmol/l

Question 20

Acute presentations of diabetes mellitus

Answer 20

ketoacidosis
rapid breakdown of fat and protein releases ketones (including acetone) and acids into bloodstream
DM type 1 and rarely type 2
can lead to coma and death

Question 21

Acute presentations of diabetes mellitus

Answer 21

hyperosmolar nonketotic state
   severe dehydration
   DM type 2
  can lead to coma and death
   hypoglycaemia
   insulin overdose, generally accidental
   can lead to coma and death
   diabetic foot
   can lead to generalised sepsis and death

Question 22

Chronic presentations of diabetes mellitus

Answer 22

Macrovascular
   ischaemic heart disease
   stroke
   peripheral vascular disease
   Microvascular
   retinopathy
   neuropathy
   nephropathy
   Cataract

Question 23

Diabetic retinopathy

Answer 23

proliferation of blood vessels in the retina
retinal haemorrhages
macular oedema
fluid exudation into retina

NB Hyperglycaemia alone can cause visual disturbance, but this is not diabetic retinopathy

Question 24

Diabetic neuropathy

Answer 24

microangiopathy of vasa nervosum
   peripheral numbness or tingling
   occasional neuropathic pain
   muscle weakness
   autonomic neuropathy
  vomiting, diarrhoea, constipation 
  impotence, incontinence, anorgasmia
  postural hypotension

Question 25

Diabetic nephropathy

Answer 25

microangiopathy of glomerular capillaries

pathology: nodular and diffuse glomerulosclerosis
clinical: chronic renal failure or nephrotic syndrome; hypertension

Question 26

Infections in diabetes mellitus

Answer 26

overall risk ratio 		1.21
   osteomyelitis 		4.39	
   septicaemia		2.45
   post-op infections	2.02
   rectal abscess		1.97	
   pyelonephritis		1.95