Definition: State of chronic hyperglycaemia,
classically associated with polyuria, polydipsia and weight loss.
DM may be primary or secondary. The secondary causes are:
- pancreatic disease
- chronic pancreatitis
- cystic fibrosis
- endocrine disease
PPG glucose correlates better with HbA1c, microvascular and macrovascular
complications (Honolulu Heart Study).
fasting serum glucose >7.0 mmol/l
2h post 75g glucose load > 11.1 mmol.l
Lispro insulin: better PPG glucose ctrl compared to human insulin (Zinman, 1997)
- Biguanides: ↓ hepatic glucose output (e.g., metformin)
- Thiazolidinediones: enhance peripheral glucose uptake.
- Insulin secretagogues: sulphonylurea (e.g., gliclazide), meglitinide (e.g., repaglinide): ↑ insulin secretion.
May induce hypoglycaemia
- Glucosidase inhibitors: reduce digestion & absorption of starch & sucrose (e.g., acarbose).
(Weyer C et al. J Clin Invest 1999;104:787-794.)
Three stages: normal→IGT→DM.
IGT: insulin secretion in response to IV glucose load falls.
DM: hepatic glucose production rises.
- hard exudates
- dot & blot haemorrhages
- cotton wool spots
- flame haemorrhages
- vitreous haemorrhage
- End stage
- family history
- low birth weight ('thrifty' phenotype)
Cardiovascular risk ↑2–4 times.
35% of end-stage renal failure, 50% of nontraumatic lower limb amputations.
"Snowflake" cataracts. Ordinary senile cataracts no increase.
Diabetic eye disease
Diabetic retinopathy, cataracts, glaucoma (rubeosis iridis),
retinal artery/vein thrombosis.
Plasma glucose (portable glucometer, ?continuous monitoring)
Implantable infusion pumps?
Refinement in islet transplant/pancreas transplant?
Vascular endothelial growth factor antagonists—diabetic retinopathy; agonists—nephropathy.
Pimagedine: inhibits formation of AGEs.
ALT-711: hypertension, CCF?
Da Qing study (Pan et al. Diabetes Care 1997;20:537-44).
Patients with impaired glucose tolerance randomised to
control, exercise only, diet only, exercise + diet.
Incidence of DM after 6y was 67.7%, 43.8%, 41.1%, 46.0%.
Results were significant (P<0.05).
Diabetes Prevention Program funded by NIH.
Examine the results of Da Qing study.
HOPE trial. There was a reduction in new diabetics in the
ramapril treated arm.
Screening for anti-islet antibodies?
UKPDS (BMJ 1998; 317:703–712, 713–719, 720–726.
Lancet 1998; 352:837–853, 854–865.)
Led by Prof Robert Turner & Prof Rury Holman at Oxford.
20 year trial, N=5102, £23 million.
Tight glycaemic control (HbA1c 7–7.9%)
improved the microvascular complication rate by 11%, irrespective of
therapeutic modality (insulin, biguanide, sulphonylurea).
There was no significant effect on macrovascular complication rate
Improved hypertensive control reduces both macro- and microvascular
complication rate, but no reduction in overall mortality.
Metformin may decrease cardiovascular complications and improve