SEATTLE -- Increases in fasting plasma glucose in non-diabetic patients appear to be caused by decreased glucose clearance rather than an increase in hepatic glucose production.
SEATTLE, April 16 -- Increases in fasting plasma glucose in non-diabetic patients appear to be caused by decreased glucose clearance rather than an increase in hepatic glucose production, investigators here reported.
The finding that hepatic glucose production slides downward as fasting plasma glucose creeps upward runs counter to current understanding of the evolution from the pre-diabetic state into full blown type 2 diabetes, acknowledged Rucha Jani, M.D., of the University of Texas Health Sciences Center in San Antonio.
"Hepatic glucose production is the biggest source of fasting plasma glucose," Dr. Jani said at the American Association of Clinical Endocrinologists meeting.
"We wanted to investigate whether that was also the case in the pre-diabetes state, and to our surprise, in these patients we found that the hepatic glucose production seemed to decrease, and it was possibly correlated with the fasting plasma glucose," said Dr. Jani.
The research also points to possible diabetes prevention strategies targeted at glucose clearance. They hypothesized that the glucose-1 transporter, an insulin-independent glucose transporter in the basal state may in the fasting state be what they term "the missing link" coupling the pre-diabetes state to type 2 diabetes.
Dr. Jani and colleagues arrived at their conclusions after studying 165 patients without type 2 diabetes, each of whom received an oral glucose tolerance test and insulin clamp with three-hour glucose. They calculated the rate of glucose appearance, glucose clearance, hepatic insulin resistance index, total glucose disposal, and insulin-stimulated glucose clearance. They used simple Pearson correlation to assess the relationship between variables.
They found that an increase in fasting plasma glucose (range 75 to 120 mg/dL, significantly correlated with an increase in body mass index (range 20-50 kg/m2, r=0.30, P
"If we can identify this missing link, we can target future therapies at the glucose transporter, and thereby prevent the progression from even before you get to impaired fasting glucose," she said.