Preoperative and Postoperative Predictors of Insulin Independence From Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVE: This study examined the preoperative and postoperative variables associated with 1 year and long-term insulin independence following total pancreatectomy and islet autotransplantation (TPIAT). METHODS: 46 TPIAT patients from 2010 to 2022 in a single hospital system were retrospectively analyzed. Pre- and postoperative variables were compared between short-term (1 year) and long-term (last follow-up after year 1) insulin-independent versus -dependent patients. RESULTS: Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed up for a median of 2.8 years (interquartile range [IQR] 1.0, 4.7). Short-term insulin independence was associated with higher median transplanted islet equivalents (IEQ) per kg (6981 vs 4493, P = .02), lower units of basal insulin on discharge (7 vs 12, P = .009), and lower rates of discharge with an insulin regimen (67% vs 100%, P = .006). Odds of short-term insulin independence increased by 80% for every 1000 increase in IEQ per kg (OR 1.80, CI 1.18-3.12, P = .005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42-0.91, P = .003) on average. Long-term insulin independence was also associated with transplanted IEQ per kg. No patient on antihyperglycemic medication before surgery achieved insulin independence. CONCLUSION: Short- and long-term insulin independence after TPIAT is associated with higher transplanted IEQ per kg and immediate postoperative variables that can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT.

Rekindling Hope for Remission: Current Impact of Diabetes for Our World's Future Health and Economy.

The individual and societal burdens of living with a chronic disease are a global issue. Diabetes directly increases health care costs to manage the disease and the associated complications and indirectly increases the economic burden through long-term complications that hinder the productivity of humans worldwide. Thus, it is crucial to have accurate information on diabetes-related costs and the geographic and global economic impact when planning interventions and future strategies. Health care systems must work with government agencies to plan national-level pre diabetes and diabetes strategies and policies. Public health services must focus on diabetes screening prevention and remission.

What Is a Honeymoon in Type 1, Can It Go into Remission?

Type 1 diabetes is a chronic autoimmune disorder that results in destruction of insulin-producing cells in the pancreas. The autoimmune process is thought to be waxing and waning resulting in variable endogenous insulin secretion ability. An example of this is the honeymoon phase or partial remission phase of type 1 diabetes, during which optimal control of blood glucoses can be maintained with significantly reduced exogenous insulin, and occasionally exogenous insulin can be temporarily discontinued altogether. Understanding this phase is important because even fairly small amounts of endogenous insulin secretion is associated with reduced risk of severe hypoglycemia and microvascular complications.

Islet Cell Therapy and Stem Cell Therapy for Type 1 Diabetes: There Will Always Be a Hope.

To date, people living with type 1 diabetes depend on external subcutaneous insulin while waiting for a cure, or a feasible method to preserve, replace, and generate fully functioning ß cells that secrete appropriate insulin in response to glucose. Current work includes evaluating renewable sources of ß cells, transplantation methods without immunosuppressives, and methods to preserve ß-cell function. Such methods include ß-cell encapsulation, scaffolding, immune modulation, gene editing, and disease-modifying therapies. The purpose of this article is to review the progress and describe ß-cell therapies over the past 5 years.

Correction: Pancreatectomy and islet cell autotransplantation.

The article "Total pancreatectomy and islet cell autotransplantation: Definitive treatment for chronic pancreatitis" (Arce KM, Lin YK, Stevens T, Walsh RM, Hatipoglu BA. Cleve Clin J Med 2016; 83:435-442) incorrectly stated that Paul Lacy and David Scharp performed research at the University of Washington at Seattle. They did their work at Washington University in St. Louis, Missouri.

Spontaneous Hypoglycemia After Islet Autotransplantation for Chronic Pancreatitis.

CONTEXT: Spontaneous hypoglycemia has been reported in patients after total pancreatectomy (TP) and islet autotransplantation (IAT) with maintained insulin independence. Details surrounding these events have not been well described. OBJECTIVE: The objective of the study was to determine the frequency and characteristics of spontaneous hypoglycemia in patients undergoing TP-IAT and/or to ascertain predictive or protective factors of its development. DESIGN: This was an observational cohort study in 40 patients who underwent TP-IAT from August 2008 to May 2014, with a median follow-up of 34 months. SETTING: The study was conducted at a single institution (Cleveland Clinic). PATIENTS: Patients included recipients of TP-IAT. INTERVENTION: The intervention included small, frequent meals in those patients who developed spontaneous hypoglycemia. MAIN OUTCOME MEASURES: Incidence of spontaneous hypoglycemia development, characteristics of the patients developing hypoglycemia, and their response to small, frequent meals were measured. RESULTS: Six of 12 patients, who maintained insulin independence, developed spontaneous hypoglycemia. The episodes could be fasting, postprandial, and/or exercise associated, with the frequency ranging from two to three times daily to once every 1-2 weeks. All patients experienced at least one episode that required external assistance, glucagon administration, and/or emergent medical attention. Patients who developed hypoglycemia had a lower median age and tended to have a lower median islet equivalent/kg body weight but a higher median total islet equivalent, body mass index, and homeostatic model assessment for insulin resistance score. All patients who received small, frequent meal intervention had improvement in severity and/or frequency of the hypoglycemic episodes. CONCLUSIONS: Spontaneous hypoglycemia is prevalent after TP-IAT. Although the underlying pathophysiology responsible for these hypoglycemia events remains to be elucidated, small, frequent meal intervention is helpful in ameliorating this condition.

Total pancreatectomy and islet cell autotransplantation: Definitive treatment for chronic pancreatitis.

In appropriately selected patients, total pancreatectomy and islet cell autotransplant controls pain and improves quality of life while often minimizing the development of overt diabetes. Multidisciplinary management and lifelong follow-up help to maximize the benefit of this procedure. This review highlights its history, indications, metabolic outcomes, and future directions.

Chronic Pancreatitis and Diabetes Mellitus.

OPINION STATEMENT: Patients with chronic pancreatitis should be screening at least annually for diabetes. Lifestyle modifications remain to be an important part of treatment for diabetic control. Unless contraindicated or not tolerated, metformin can be initiated and continued concurrently with other anti-diabetic agents or insulin. All anti-diabetic agents should be used based on their physiology and adverse effect profiles, along with the metabolic status of patients. Insulin therapy should be initiated without delay for any of the following: symptomatic or overt hyperglycemia, catabolic state secondary to uncontrolled diabetes, history of diabetic ketoacidosis, hospitalization or acute exacerbation of pancreatitis, or hyperglycemia that cannot be otherwise controlled. Dose adjustment should be done conservatively as these patients are more likely to be insulin sensitive and have loss of counter regulatory hormones. Insulin pump and continuous glucose monitoring should be considered early during therapy in selected patients. For patients undergoing total pancreatectomy or extensive partial pancreatectomy, evaluations to determine the eligibilities for islet cell autotransplantation should be considered.

Factors associated with islet yield and insulin independence after total pancreatectomy and islet cell autotransplantation in patients with chronic pancreatitis utilizing off-site islet isolation: Cleveland Clinic experience.

CONTEXT: Total pancreatectomy (TP) with islet cell autotransplantation (IAT) can reduce or prevent diabetes by preserving beta cell function and is normally performed with on-site isolation laboratory facilities. OBJECTIVE: We examined factors associated with islet yield and metabolic outcomes in patients with chronic pancreatitis undergoing TP-IAT. We report our experience of TP-IAT with an off-site islet isolation laboratory. PATIENTS AND METHODS: Data (August 2008 to February 2014) were obtained from a TP-IAT database which included information from medical records, clinic visits, questionnaires, and follow-up telephone calls. Each patient was assessed with pre- and postoperative 5-hour mixed-meal tolerance tests for metabolic measurements and with serial glycosylated hemoglobin (HbA1c) determinations. RESULTS: Thirty-six patients with a mean age of 38 years (range, 16-72 y) underwent TP-IAT for different etiologies. At a median follow-up time of 28 months (range, 3-66 mo), 12 patients were insulin independent and 24 patients were on at least one insulin injection a day. Postoperatively, C-peptide levels ≥0.3 ng/mL were present in 23/33 (70%) of the patients, with a median fasting C-peptide value of 0.8 ng/mL (range, <0.2-1.5 ng/mL). Those who were insulin independent were more likely to be female (P = .012), have normal morphology on pre-operative pancreatic imaging (P = .011), and have significantly higher median islet yield (6845 islet equivalent numbers [IEQ]/kg, n = 12 vs 3333 IEQ/kg, n = 24; P < .001). CONCLUSIONS: IAT after TP performed in our facility with an off-site islet isolation laboratory shows islet yield and rates of insulin independence that are comparable to other large centers with on-site laboratories.

DPP-4 INHIBITOR THERAPY IN PATIENTS AFTER PANCREATIC TRANSPLANT.

OBJECTIVE: Management of new onset hyperglycemia after pancreas transplantation (PT) is not well studied. There is a lack of information on effective and safe management options for hyperglycemia after PT. We tested the hypothesis that early intervention for hyperglycemia using a dipeptidyl peptidase-4 (DPP-4) inhibitor prolongs insulin-free graft function in patients after PT. METHODS: Twenty-six patients who developed noninsulin-dependent hyperglycemia at least 1 year after PT met the inclusion criteria for this retrospective chart review. Sitagliptin, a DPP-4 inhibitor, was a commonly used therapy for hyperglycemia after PT due to its wide availability and coverage. The standard therapy group included patients who did not receive any oral or noninsulin injection therapy until insulin was clearly required to control hyperglycemia. The intervention group included patients who had received sitagliptin soon after hyperglycemia developed. The median follow-up period was 45 months. The time to hyperglycemia from 1 year after PT and time to insulin requirement after hyperglycemia development were compared between these 2 groups. RESULTS: The time to hyperglycemia after PT was not different between the groups, but the time to insulin requirement was significantly longer in the intervention group compared with the standard therapy group (P<.001). After adjusting for body mass index (BMI), the difference remained significant (P<.001). CONCLUSION: Early treatment of hyperglycemia after PT with a DPP-4 inhibitor such as sitagliptin prolongs the time to insulin therapy compared with a standard observation approach. Prospective studies are needed to further investigate this observation.

Hyponatremia and the Thyroid: Causality or Association?

Thyroid disorders, particularly hypothyroidism, have historically been implicated in the development of serum hyponatremia. However, in more recent years, this paradigm has been challenged, and it has been suggested that the link between hypothyroidism and hyponatremia may merely be an association. This review will focus on the thyroid and its link with serum hyponatremia, and review the available literature on the topic.

Serum IGF-1 in the diagnosis of acromegaly and the profile of patients with elevated IGF-1 but normal glucose-suppressed growth hormone.

OBJECTIVE: To report the utility of insulin-like growth factor-1 (IGF-1) as a single biomarker for establishing the diagnosis of acromegaly and to examine the clinical and biochemical profile of patients with an elevated IGF-1 in whom a diagnosis of acromegaly could not be confirmed by means of the oral glucose tolerance test (OGTT). METHODS: Between the years 1999 and 2010, we identified 101 patients who underwent pituitary surgery and had histologically proven somatotroph adenomas (Group 1, Gr 1). We selected 149 patients with non-growth hormone (GH) secreting pituitary macroadenomas (Gr 2, n = 97) and microadenomas (Gr 3, n = 52) to serve as control subjects. In addition, we identified 34 patients with elevated IGF-1values in whom acromegaly could not subsequently be proven by the OGTT (Gr 4). RESULTS: IGF-1 was elevated in all patients with acromegaly prior to therapy with a median (range) standard deviation score (SDS) of +9.52 (+2.34 to +9.2), compared to SDS -1.46 (-2.91 to +2.17) and -1.22 (-2.8 to +1.58) in Gr 2 and 3, respectively (P<0.001). IGF-1 SDS values were +3.28 (+2.05 to +6.1), and IGF-1 was less than twice the upper limit of normal in all patients in Gr 4. OGTT was performed in 51 of the 101 acromegalic patients. The nadir GH in these patients was 4.01 (0.2 to 46.7) in comparison with 0.2 (<0.05 to 0.6) in Gr 4 (P<0.001). CONCLUSION: Elevated IGF-1 levels, alone, are sufficient to establish a diagnosis of acromegaly in the majority of clinically suspected cases. The OGTT may be useful to obtain corroborative evidence when there is modest elevation of IGF-1 with absent or equivocal clinical features.

Cushing's syndrome.

Cushing's syndrome (CS) results from prolonged exposure to elevated endogenous cortisol. Majority of cases are caused by ACTH, pituitary, or ectopic origin. Primary adrenal hypersecretion is 15-20% caused by adenomas, carcinomas (ACC), and rarely by nodular adrenocortical disease. CS presents with all typical features. Commonly recommended initial testing are urinary free cortisol, late-night salivary cortisol, and 1-mg overnight dexamethasone suppression test (DST). Imaging is the key to diagnosis. CS continues to pose diagnostic and therapeutic challenges; life-long follow-up is mandatory.

Postradiation therapy hypopituitarism.

The increasing use of radiation treatment for head and neck cancers and other tumors, including pituitary adenomas, from the mid-20th Century onwards led to the recognition that pituitary function may be affected - often leading to some degree of pituitary insufficiency. Our knowledge is mostly based on observational or retrospective rather than randomized prospective studies. The various axes may be impacted at the hypothalamic or pituitary levels, or both. Some axes - the somatotropic and gonadotropic - appear to be especially vulnerable to radiation damage and may be affected quite early, whereas posterior pituitary function is rarely affected. Increased use of stereotactic radiosurgery, which focuses the radiation dose on the abnormal tissue, may be expected to reduce the impact on normal pituitary function, but such studies that are available are, as yet, relatively short term. Prospective studies of the effect of stereotactic radiosurgery on pituitary function would be valuable.

A case of pancreatic islet cell transplantation in a patient with situs ambiguous: anatomical and radiological considerations.

Pancreatic islet cell transplantation is an evolving treatment of severe, refractory type 1 diabetes that has been gaining more use, particularly after one year rates of insulin independence post-transplantation were found to approach 80% under the Edmonton protocol. Islet cell transplantation involves percutaneous delivery of harvested allogeneic ß cells into the portal venous circulation for implantation into the liver. We present the case of a 35-year-old woman with type 1 diabetes and situs ambiguous with left isomerism and resultant variant anatomy of her portal venous anatomy who underwent islet cell transplantation, which, to our knowledge, has not been previously reported.