Somatostatin analogues in diabetes mellitus.
Growth hormone (GH) has long been considered to have importance in diabetes. With poor control in Type 1 diabetes GH levels are high and may aggravate poor metabolic control. Pharmacological suppression of GH release at this stage might reverse the metabolic changes, with the possible added benefit of lower plasma insulin concentrations. Diabetic patients with life-long GH deficiency rarely develop retinopathy, while pituitary ablation in patients with retinopathy often leads to improvement. Growth hormone release inhibiting factor, somatostatin, has a short plasma half-life, and multiple effects on the endocrine system and on the gastrointestinal tract, making it unsuitable for clinical use as a GH suppressant. Long-acting analogues have a long half-life, but remain non-specific in their effects. In Type 2 diabetes the analogue Octreotide suppresses insulin and glucagon release, leaving glucose levels either unchanged or somewhat elevated. Gastrointestinal side-effects have been common, but may diminish with long-term treatment. In Type 1 diabetes insulin requirement is decreased by Octreotide, but as in Type 2 diabetes GH suppression has been observed consistently only when the drug was given at bed-time. The decrease in insulin requirement may reflect suppression of glucagon release and/or gut effects. Amelioration of the 'dawn phenomenon' has not proved possible, and hypoglycaemia has proved a particular problem with Octreotide given subcutaneously at night. The lack of effective GH suppression (particularly in patients with proliferative retinopathy), lack of specificity, and the gut and hypoglycaemic side-effects, argue strongly against a clinical role for the current somatostatin analogues in diabetes mellitus.
Davies
R R
RR
Ninewells Hospital and Medical School, Dundee, UK.
Turner
S J
SJ
Alberti
K G
KG
Johnston
D G
DG
D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000502:physiology; D006801:Humans; D015282:Octreotide / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D013004:Somatostatin; D013006:Growth Hormone; D015282:Octreotide