Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics.

Forty-eight out of 53 non-insulin-dependent diabetic identical twin pairs were concordant for diabetes. In the five discordant pairs the diabetic twin had only recently been diagnosed. Oral glucose tolerance tests were carried out on the unaffected twins of the five pairs and on matched controls. Fasting concentrations of blood glucose (5.5 +/- 0.6 v 3.7 +/- 0.3 mmol/l; 99.1 +/- 10.8 v 66.6 +/- 5.4 mg/100 ml), haemoglobin A1 (mean 9.1%, range 8.8-9.2% v mean 7.9%, range 7.4-8.4%), lactate, alanine, and glycerol (0.090 +/- 0.017 v 0.045 +/- 0.008 mmol/l); and the lactate: pyruvate ratio were significantly higher in the twins than controls. After glucose challenge blood glucose, lactate, alanine, and glycerol concentrations and lactate: pyruvate ratio were increased in the twins. Insulin response was severely impaired, being almost absent in four of the five twins. The non-diabetic members of the discordant non-insulin-dependent diabetic pairs showed noticeable metabolic abnormalities which would later presumably deteriorate to frank diabetes. These findings, taken with the high concordance rate for non-insulin-dependent diabetic twins, suggest that non-insulin-dependent diabetes is predominantly, possibly entirely, inherited.