Determinants of glucose control in patients with chronic pancreatitis

Abstract

Aims/hypothesis Diabetes frequently develops in patients with chronic pancreatitis (CP). Partial pancreatectomy has emerged as a treatment option for such patients. We addressed whether the development of diabetes in CP patients is related to pancreatic beta cell area or clinical variables, and which factors predict the diabetes risk after partial pancreatectomy. Methods Fractional beta cell area was determined in pancreatic tissue samples obtained from 114 CP patients undergoing pancreatic surgery and related to measures of glucose control, as well as clinical and anthropometric data. Seventy-four patients without diabetes at the time of surgery were contacted again 2.5±1.0 years after partial pancreatectomy in order to obtain information about the post-operative development of diabetes. Results In the surgical samples in the whole cohort, pancreatic beta cell area was 0.40±0.06% in patients with and 0.64±0.06% in those without previously known diabetes (p=0.039). There was an inverse non-linear relationship between pancreatic beta cell area and fasting glucose concentrations (r=0.29) as well as HbA 1c levels (r=0.36). Nineteen out of 74 previously normoglycaemic patients (26%) developed diabetes over an average period of 2.5 years of follow-up. Pre-operative fasting glucose levels, HbA 1c and BMI were identified as predictors of diabetes after partial pancreatectomy. However, pancreatic beta cell area did not differ in those who subsequently developed diabetes (0.66±0.15%) and those who did not (0.62± 0.08%, p=0.45). Conclusions/interpretation Hyperglycaemia in CP patients is associated with reduced beta cell area. However, reduced beta cell area does not predict the development of diabetes, suggesting that other factors are more important determinants of alterations in glucose metabolism in patients with CP.

Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans

“…Thus, the curve-linear relationship between pancreatic beta cell area and fasting glucose concentrations was shifted upwards by~0.44 mmol/l (8 mg/dl) in individuals with the lowest insulin sensitivity compared with the most insulin-sensitive individuals. This is consistent with previous studies showing that a modest increase in BMI confers a greater risk for developing diabetes after a partial pancreatectomy even in a predominantly lean population of patients with chronic pancreatitis [6]. Interestingly, the degree of insulin sensitivity appeared to be less important for the 120 min post-challenge glucose concentrations, indicating that the glycaemic response to the oral glucose load was primarily determined by the extent of pancreatic beta cells.…”

“…In fact, the manifestation of diabetes in lean patients without a typical history of type 2 diabetes has been considered as a clinical indication of pancreatic carcinoma [4]. At present, studies on the pathogenesis of pancreatic diabetes in humans are relatively sparse, but progressive beta cell destruction is held to be the major underlying cause [5,6]. Whether insulin resistance is involved in the development of diabetes in such patients is not known, given the paucity of studies in this area.…”

“…These studies revealed a reduction in pancreatic beta cell area of~30-40% in patients with chronic pancreatitis [5]. Furthermore, a retrospective case series of 114 patients with chronic pancreatitis established an inverse curve-linear relationship between fasting glucose concentrations and beta cell area [6]. However, by design information on insulin secretion and insulin sensitivity was not available in these studies.…”

Body Mass Index and Outcomes from Pancreatic Resection: a Review and Meta-analysis

“…81,82 In all, 17 studies were included in the final set (Table 1). [14][15][16][17][21][22][23][24][83][84][85][86][87][88][89][90][91] All primary studies reported retrospective analyses of prospectively maintained databases, suggesting that selection bias may exist in this body of literature. Our 17 study cohort included a total of 4,045 patients, though BMI information was reported heterogeneously.…”

Brittle Diabetes: A Contemporary Review of the Myth and Its Realization

“…Brittle diabetes is also frequently developed in patients with chronic pancreatitis after partial pancreatectomy and its development is partially related to reduced pancreatic beta-cell area , as well as other clinical variables, i.e. pre-operative fasting glucose levels, HbA1c and body mass index (Schrader et al, 2010). This is further highlighted by the fact that different surgical procedures have an unequal impact on glucose control.…”