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A total of 220 non-insulin-dependent diabetics aged over 45 (139 with a history of chlorpropamide-alcohol flushing and 81 without such a history) were examined for the prevalence of large-vessel disease. Large-vessel disease was significantly more common in the group without a history of flushing (41% v 24% of the two groups respectively; p < 0.05). A history of myocardial infarction was found in 14 (17%) of the patients without flushing but in only 10 (7%) patients with flushing. Similar differences were detected in the prevalences of angina, intermittent claudication, and absent foot pulses. There were, however, no significant differences in the prevalence of cerebrovascular disease or hypertension between the two groups. These results suggest that patients with non-insulin-dependent diabetes who flush in response to chlorpropamide and alcohol are significantly less likely to develop large-vessel disease than those who do not. Hence such flushing is probably related to the pathogenesis not only of small-vessel but also of large-vessel disease.

A simple test was devised to identify people susceptible to chlorpropamide-alcohol flushing (CPAF). Subjects were given a placebo tablet, followed by sherry 12 and 36 hours later. They then received a chlorpropamide tablet and sherry again after 12 and 36 hours. This single-dose challenge test was given to non-insulin-dependent diabetics, insulin-dependent diabetics, and normal subjects. CPAF was common in the non-insulin-dependent diabetics but rare in the other groups. When the test was used in identical twins and families of affected subjects CPAF appeared to be a dominantly inherited trait. We conclude that facial flushing after alcohol in people taking chlorpropamide is related to non-insulin-dependent diabetes, especially when there is a strong family history of diabetes, but not to insulin-dependent diabetes. It is a dominantly inherited trait.

The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome.

Beta cell function has been studied by measurement of C-peptide responses to intravenous glucagon in 11 diabetics with advanced complications and compared with nine long-term diabetics without complications. The majority had no C-peptide responses, but there was evidence of beta cell function in one patient from each group. These observations suggest that some factor other than continuing beta cell function is involved in the complications of insulin-requiring diabetics.