Evolution of -Cell Replacement Therapy in Diabetes Mellitus: Islet Cell Transplantation

Abstract

Diabetes mellitus remains one of the leading causes of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention, approximately 23.6 million people in the United States are affected. Of these individuals, 5 to 10% have been diagnosed with Type 1 diabetes mellitus (T1DM), an autoimmune disease. Although it often appears in childhood, T1DM may manifest at any age, leading to significant morbidity and decreased quality of life. Since the 1960s, the surgical treatment for diabetes mellitus has evolved to become a viable alternative to insulin administration, beginning with pancreatic transplantation. While islet cell transplantation has emerged as another potential alternative, its role in the treatment of T1DM remains to be solidified as research continues to establish it as a truly viable alternative for achieving insulin independence. In this paper, the historical evolution, procurement, current status, benefits, risks, and ongoing research of islet cell transplantation are explored.

Anti-inflammatory Interventional Strategies to Promote Islet Transplantation Outcomes

“…While exogenous insulin therapy remains the most common and effective standard for day-to-day control of Type 1 Diabetes (T1D), recurring incidences of hypoglycemic episodes and long-term complications such as retinopathy, neuropathy, nephropathy, and cerebrovascular/cardiovascular diseases necessitate transplantation of either whole pancreas or pancreatic islets as a more effective treatment in a high percentage of patients [1][2][3][4][5][6]. Of the two, clinical islet transplantation is less invasive, being associated with a 20% lower morbidity risk compared to whole pancreas transplantation.…”

Total Pancreatectomy and Islet Autotransplantation for Chronic Pancreatitis

“…IAT candidates are counseled that exocrine deficiency may be made worse or induced by TP. Exocrine deficiency may be responsible for the more erratic blood sugar control in pancreatic diabetes than type 1 diabetes because of erratic absorption making the predicted insulin dose more difficult to calculate (Jahansouz et al, 2011;Robertson, 2010a;Robertson, 2010b). However, at least one group has reported that diabetic control after TP (for a variety of reasons) without IAT is equivalent to that of patients with type 1 diabetes in their clinic (Jethwa et al, 2006).…”

“…The largest series published to date on patients undergoing pancreatectomy and IAT have come from the University of Minnesota (Farney et al, 1991;Gores et al, 1992;Gruessner et al, 2004;Jie et al, 2005;Najarian et al, 1979;Najarian et al, 1980;Sutherland et al, 1978;Sutherland et al, 1980a;Sutherland et al, 2004a;Sutherland et al, 2009a;Sutherland et al, 2009b;Sutherland et al, 2011b;Wahoff et al, 1995a) (>400), the University of Cincinnati (Ahmad et al, 2005;Rodriguez et al, 2003;Sutton et al, 2010) (>100), the University of Leicester (Clayton et al, 2003;;Garcea et al, 2009;White SA et al, 1998;White SA et al, 2001;Webb et al, 2008) (>50 cases), but there are many center that are building their series (Argo et al, 2008;Berney T et al, 2000;Desai et al, 2011;Dixon et al, 2008;Jahansouz et al, 2011;Takita et al, 2010;Takita et al, 2011b;Valente et al, 1986) The reports from these centers largely focus on metabolic outcomes, QOL, and pain reduction., but there are many publications on specialized aspects of TP-IAT as have been referenced in this chapter.…”

“…Islet allografts are currently associated with a high rate of early insulin independence, but after 1 year insulin-independence rates have declined relatively rapidly in the CITR analyses overall (CITR; 2009) and at most (Jahansouz et al, 2011) but, more recently, not all (Bellin et al, 2008b) institutions,. The 2008 analysis of islet auto-transplants (IATs) done at the University Of Minnesota over a 30 year period in those who achieved function showed to be relatively durable compared to the islet allografts, despite a lower beta-cell mass (Bellin et al, 2008b).…”

“…Indeed, islet allograft recipients who remain insulin dependent but have β-cell function and are C-peptide positive are metabolically more stable and less prone to hypoglycemic unawareness than those who have no β-cell function ( Jahansouz et al, 2011;Paty et al, 2006;Robertson, 2010b;Ryan et al, 2002;Ryan et al, 2005). Furthermore, the risk of secondary complications is less in diabetics who receive or are C-peptide-positive (Jahansouz et al, 2011;Johansson et al, 2000;Kamiya et al, 2004). By extrapolation, IAT recipients who are C-peptide-positive, even with an insulin requirement, have a metabolic advantage (Dong et al, 2011).…”