Functional Assessment of Pancreatic β-Cell Area in Humans

Abstract

OBJECTIVEβ-Cell mass declines progressively during the course of diabetes, and various antidiabetic treatment regimens have been suggested to modulate β-cell mass. However, imaging methods allowing the monitoring of changes in β-cell mass in vivo have not yet become available. We address whether pancreatic β-cell area can be assessed by functional test of insulin secretion in humans.RESEARCH DESIGN AND METHODSA total of 33 patients with chronic pancreatitis (n = 17), benign pancreatic adenomas (n = 13), and tumors of the ampulla of Vater (n = 3) at various stages of glucose tolerance were examined with an oral glucose load before undergoing pancreatic surgery. Indexes of insulin secretion were calculated and compared with the fractional β-cell area of the pancreas.RESULTSβ-Cell area was related to fasting glucose concentrations in an inverse linear fashion (r = −0.53, P = 0.0014) and to 120-min postchallenge glycemia in an inverse exponential fashion (r = −0.89). β-Cell area was best predicted by a C-peptide–to–glucose ratio determined 15 min after the glucose drink (r = 0.72, P < 0.0001). However, a fasting C-peptide–to–glucose ratio already yielded a reasonably close correlation (r = 0.63, P < 0.0001). Homeostasis model assessment (HOMA) β-cell function was unrelated to β-cell area.CONCLUSIONSGlucose control is closely related to pancreatic β-cell area in humans. A C-peptide–to–glucose ratio after oral glucose ingestion appears to better predict β-cell area than fasting measures, such as the HOMA index.

Determinants of glucose control in patients with chronic pancreatitis

“…Because of the frequent use of glucose-lowering medication in the patients with diabetes studied herein, it is likely that glucose concentrations of these patients would have been even higher after a drug-washout period. This might explain why the associations between beta cell area and glycaemic control found in this study were weaker than those described in the previous study [34].…”

“…Consistent with such reasoning, the inverse relationship between beta cell area and glycaemic control was no longer detectable when the groups of patients with and without diabetes were studied separately. The present results are in support of our previous study about functional predictors of beta cell area in humans [34]. In that study, an even closer association between glycaemia and beta cell area has been found.…”

“…Furthermore, beta cell area can vary extensively within the pancreas, and this factor might be of particular relevance in patients with CP, in whom different parts of the organ might be unequally affected by the inflammatory process. In this regard, some studies have also reported a preferential abundance of beta cells in the pancreatic tail [11], but this has not been confirmed by others [7,34]. Nevertheless, the error implied by these factors might have contributed to the great variance in beta cell area observed in this study.…”

Increment of C-peptide after glucagon injection determines the progressive nature of Japanese type 2 diabetes: A long-term follow-up study

“…The duration of diabetes at baseline was significantly longer in the insulin-treated group than in the non-insulin-treated group. There was no significant dif- betes [3], and various antidiabetic treatment regimens have been postulated to modulate β-cell mass. To the best of our knowledge, no earlier studies have comprehensively examined the influence of clinical characteristics on the annual decline of β-cell function.…”

A new view of the beta cell

“…These are based on correlations between functional insulin secretion measurements and beta cell mass [4]. Furthermore, establishment of the beta cell mass by morphometry on biopsies may be grossly misleading owing to the heterogeneity of islet distribution in the organ.…”