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The basal plasma insulin and glucose concentrations of 12 diet-treated maturity-onset diabetics were measured at minute intervals for 2 h. Brief, irregular oscillations (mean period 8.8 min) in plasma insulin were superimposed on longer term fluctuations (greater than 30 min). Time series analysis demonstrated a synchronous plasma glucose oscillation (mean amplitude 0.03 mmol/L) associated with short insulin cycles. The glucose changes seen in diabetic subjects were similar to the short plasma insulin cycles (less than 10 min) observed in normal subjects. In contrast, the longer plasma insulin cycles (greater than 10 min) of normal subjects were associated with a plasma glucose oscillation that rose before the end of the cycle. The demonstration of insulin oscillations independent of preceding plasma glucose changes in both normal and diabetic subjects suggests a pancreatic oscillating mechanism of "pacemaker". The associated glucose changes may reflect the entrainment, by the insulin cycles, of glucose production or utilization.

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.

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