Diabetes mellitus

Definition: State of chronic hyperglycaemia, classically associated with polyuria, polydipsia and weight loss.

Causes

DM may be primary or secondary. The secondary causes are:

Diagnosis

EITHER
fasting serum glucose >7.0 mmol/l
OR
2h post 75g glucose load > 11.1 mmol.l

PPG glucose correlates better with HbA1c, microvascular and macrovascular complications (Honolulu Heart Study).

Treatment

Insulins

Lispro insulin: better PPG glucose ctrl compared to human insulin (Zinman, 1997)

Oral anti-hyperglycaemics

Pathophysiology

Type 2

(Weyer C et al. J Clin Invest 1999;104:787-794.) Three stages: normal→IGTDM.
IGT: insulin secretion in response to IV glucose load falls. DM: hepatic glucose production rises.

Complications

Microvascular

Diabetic retinopathy

Risk factors

Type 2

  1. family history
  2. low birth weight ('thrifty' phenotype)
  3. age
  4. obesity

Macrovascular

Cardiovascular risk ↑2–4 times. 35% of end-stage renal failure, 50% of nontraumatic lower limb amputations.

Neuropathic

Other

"Snowflake" cataracts. Ordinary senile cataracts no increase.

Diabetic eye disease

Diabetic retinopathy, cataracts, glaucoma (rubeosis iridis), retinal artery/vein thrombosis.

Treatment

Insulin Sulphonylureas Biguanides PPARγ activators

The Future

Urine glucose 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? Anti-obesity medication.

Prevention

Primary prevention

Da Qing study (Pan et al. Diabetes Care 1997;20:537-44). N=577.

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?

Secondary prevention

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 or mortality.

Improved hypertensive control reduces both macro- and microvascular complication rate, but no reduction in overall mortality.

Metformin may decrease cardiovascular complications and improve mortality.

Tertiary prevention