**3. Clinical assessment of beta cell function**

Monitoring graft function is a major concern in clinical management of islet recipients since islet graft dysfunction in both acute phase after transplant and chronic phase is an obstacle to its widespread use as a standard care for type 1 diabetes. Furthermore, isolated islets are transplanted via the portal vein into the liver, making it difficult to employ biopsy examina‐ tion of engrafted islets. Hence, several methodologies to predict islet graft function indirect‐ ly have been proposed. In this section, indices currently available for clinical assessment of islet graft function are discussed (Table 5).

value for insulin independence and elimination of hypoglycemia [118]. In addition, SUITO

Beta Cell Function After Islet Transplantation http://dx.doi.org/10.5772/ 52952 181

C-peptide per glucose ratio (CP/G) is also a simple technique to predict islet graft function using blood glucose and C-peptide, similar to the SUITO index [120]. To correct islet graft function in patients with renal dysfunction, C-peptide/glucose\*creatinine ratio has also been proposed. University of Miami group showed that CP/G correlated with 90min glucose level

This scoring system uses data on fasting blood glucose, HbA1c, stimulated C-peptide, and absence of insulin or oral diabetic medication, that cover multiple aspect of glycemic control in islet recipients [121]. Correlation between β score and 90 min glucose level after mixed

Transplant estimated function (TEF) is calculated by a formula using daily exogenous insu‐ lin requirements and HbA1c, that are routinely measured at clinic, eliminating glucose stim‐ ulation test when compared to β score [122]. TEF correlated well with β score and insulin

Transplanted functional islet mass (TFIM) model is a recently proposed index that is aimed to guide the decision to use a specific islet preparation [123]. TFIM model is composed of transplanted islet volume, increment of insulin secretion, cold ischemia time and exocrine

Functional mass of transplanted islets can be observed by the combination of the radioiso‐ tope-labeled grafts using 18F-fluorodeoxyglucose ([18F]FDG) and positron emission tomog‐ raphy with computed tomography (PET/CT) [124, 125]. Although this technique is only applicable to capture early phase of transplantation up to 60 min after transplant, islet graft loss as well as transplanted islet distribution in the liver can be observed. Nano-iron particle also visualizes engrafted islet mass using magnetic resonance imaging (MRI) and allows

tissue volume transplanted, and can predict islet graft function.

longer follow-up when compared to PET/CT technique [126, 127].

index allows extensive link to quality of life in islet recipients [119].

*3.1.4. C-peptide/glucose ratio and C-peptide/glucose\*creatinine ratio*

and β score [120].

meal tolerance test has also been reported.

response to arginine stimulation test.

*3.1.5. β score*

*3.1.6. TEF*

*3.1.7. TFIM model*

**3.2. Clinical image study**

#### **3.1. Blood tests and clinical indices**

### *3.1.1. Glucose tolerance/stimulation test*

Glucose tolerance test (GTT) is a basic assessment method to diagnose diabetes although glucose stimulation; in itself has risk of artificial hyperglycemia for type 1 diabetic patients. Baidal et al reported that acute insulin/C-peptide release, mixed meal stimulation index, time-to-peak C-peptide, 90min glucose level and area under the curve of glucose values could predict islet dysfunction [113]. Arginine stimulation test is also useful for the evalua‐ tion of islet graft function. Glucose-potentiation slope and the maximal response in arginine stimulation test were significantly associated with β cell secretory capacity in a report from University of Pennsylvania group [114].

#### *3.1.2. HYPO score and LI*

Hypoglycemic (HYPO) score and lability index (LI) are calculated based on patients' jour‐ nals of self-monitoring blood glucose (SMBG) for a month, providing a link to graft function through the quality of glycemic control [115]. These assessment tools are beneficial since a major endpoint of clinical allogeneic islet transplantation is to prevent hypoglycemic events; however, HYPO and LI calculations require a number of glucose measurements and hence are only calculated on a monthly or yearly basis using a complex scoring system.

#### *3.1.3. SUITO index*

A simple evaluation method using fasting blood glucose and C-peptide levels has been pro‐ posed, called secretory unit of islet transplant objects (SUITO) index [116]. The SUITO index was originally developed using the concept of the homeostasis model assessment for insulin secretion (HOMA-β) model, where healthy person has 100 of SUITO index. The calculation uses serum C-peptide levels instead of insulin levels, since islet recipient may be administer‐ ing exogenous insulin during graft dysfunction and overlapped measurement of endoge‐ nous and exogenous insulin amounts are avoided [117]. SUITO index can provide reference value for insulin independence and elimination of hypoglycemia [118]. In addition, SUITO index allows extensive link to quality of life in islet recipients [119].
