In a 5-12 year follow-up study of 288 subjects with impaired glucose tolerance after a 100-g glucose load, 48 worsened to overt Type 2 (non-insulin-dependent) diabetes with the elevation of fasting blood glucose. The initial level of blood glucose was a major predictor of subsequent worsening to diabetes. In addition, subjects with a lower insulin response to glucose showed a higher incidence of worsening to the disease, irrespective of blood glucose levels. Multivariate analysis indicated that a diminished insulin response and a high maximal body weight index, as well as a high level of fasting and 2-h glucose values at the initial 100-g oral glucose tolerance test were significant independent risk factors for the development of diabetes in Japanese subjects.

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To clarify the mechanism of hyperinsulinism of hepatic cirrhosis, plasma insulin and C-peptide levels before and after oral glucose loads were measured in 34 patients with cirrhosis, 15 patients with chronic hepatitis, and 25 normal subjects. While plasma immunoreactive insulin (IRI) levels during oral glucose tolerance testing (OGTT) were significantly increased in cirrhotics, plasma immunoreactive C-peptide (CPR) levels were elevated slightly. The C-peptide to insulin ratio throughout OGTT was significantly smaller in cirrhotics than in normal subjects (P less than 0.01). A decreased hepatic insulin degradation rate has been suggested to one of the main causes of hyperinsulinism in hepatic cirrhosis. The ratio of the difference between basal and 30-min CPR values and basal and 30-min OGTT blood glucose values [delta CPR: delta BS(30)'] as well as the delta IRI: delta BS(30') ratio was significantly decreased in cirrhotics (P less than 0.01). These results indicate that insulin secretion in response to a glycemic stimulus is reduced in cirrhotics. Both the ratios of the sums of six IRS and CPR values of OGTT (sigma CPR: sigma IRI) and delta CPR: delta BS(30') and sigma CPR: sigma BS(30') were found in inverse relationship with indocyanine green retention rate in cirrhotics.

In order to study the role of the sympathetic nerves in the regulation of glucagon and insulin secretion, the distal stump of the left splanchnic nerve was electrically stimulated at the diaphragmatic level in the anesthetized dog under bilateral ligation of the adrenal veins. During stimulation, plasma glucose concentration rose rapidly, and pancreatic vein plasma concentration of glucagon increased along with pancreatic vein blood flow, indicating a greater output of glucagon. Insulin output in pancreatic vein plasma was slowly elevated despite continued stimulation. Pretreatment with propranolol resulted in a decline of the basal output of both glucagon and insulin and in their marked initial fall at the onset of the stimulus. However, glucagon output still showed a vigorous increase during neural stimulation whereas insulin output remained totally suppressed, but showed a rebound rise after cessation of stimulation. Pretreatment with phentolamine evoked an enhancement in both basal output of insulin and its response to splanchnic stimulation, but did not exert any marked effect on glucagon output. Pretreatment with atropine inhibited the basal output of glucagon and insulin, but the response of insulin output to splanchnic stimulation was not suppressed, thus excluding the possibility that activation of aberrant parasympathetic nerve fibers located in the splanchnic nerve would be responsible for the delayed increase in insulin release. The present results indicate that glucagon secretion may be regulated by different receptor mechanisms from those involved in insulin release following sympathetic activation.