Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis

Abstract

Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis. The outcome and potential benefits for pre-diabetic and diabetic patients are less well established. Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control: diabetes mellitus (DM) (n=5, 15%), pre-DM (n=11, 32%) and non-DM (n=18, 54%). Pre-operative fasting c-peptide was detectable and similar in all 3 groups. Islet yield in the DM group was comparable to pre-DM and non-DM groups (median islet equivalents [IEQ] was 191,800, 111,800, and 232,000IEQ, respectively). Patients received islet mass of over the target level of 2000IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group: 45% (5/11) and 60% (3/5) for a combined 50% (8/16) rate, respectively, compared to 83% (15/18) for the non-DM group. At 1 year, fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in non-DM. Islet transplantation failed (negative c-peptide) only in 1 patient. Pre-operatively, all patients experienced pancreatic pain with daily opioid dependence in 60% to 70%. Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms. Diabetic patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT, with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted islets. Not surprisingly, endocrine outcomes for diabetic and pre-diabetics patients are substantially worse than in those with normal pre-operative glucose control.

Metabolic measures before surgery and long-term diabetes outcomes in recipients of total pancreatectomy and islet autotransplantation

“…Although there is a substantial overlap on baseline measures between the groups who were insulin independent and dependent, our results are consistent with other recent studies 33,39 showing that having abnormal glycemia (prediabetes HbA1c or fasting blood glucose levels) appears to convey a very high likelihood for an individual patient to remain insulin dependent after surgery (Figure 2), and thus proceeding to surgery before progression to prediabetes is likely desirable. Recipients with high BMI, high stimulated blood glucose levels, or low estimated IEQs/kg (<2500 IEQs/kg) also appeared to have a low likelihood of insulin independence, and these measures could also be signs for poor metabolic outcomes.…”

Effectiveness of Intraoperative Versus Dedicated Islet Cell Laboratory Isolation for Total Pancreatectomy With Islet Autotransplant

“…Patients with diabetes or prediabetes before TPIAT have been shown to have fewer isolated and transplanted islets and worse metabolic outcomes than preoperative nondiabetics. 14 Similarly, we found that patients with preoperative diabetes yielded lower IEQ than nondiabetic patients, although this was only statistically significant in the intraoperative group. One year fasting, C-peptides were also lower in preoperative diabetics than nondiabetics; however, this was not statistically significant.…”

What Is New with Total Pancreatectomy and Autologous Islet Cell Transplantation? Review of Current Progress in the Field

“…Gradually, emphasis shifted from insulin independence to better control of DM and avoiding the subsequent brittleness [ 12 ]. Recently, there have been reports of this procedure offered to current diabetic patients showing advantages in management [ 13 ].…”

“…The presence of pre-diabetes defined by the American Diabetic Association (fasting plasma glucose between 100 and 125 mg/dl (5.6–6.9 mmol/L) or HbA1c between 5.7% and 6.4% without any pharmacological support), was correlated with a significantly lower chance for insulin independence at 1 year, 13% vs. 53% in patients with normal glucose control, which has major clinical implications. Information about HbA1c and fasting blood glucose are easily obtained to help in preoperative decisions and set up realistic expectations about glucose control postoperatively [ 13 ].…”