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Purpose of Review Ketosis-prone diabetes or Flatbush diabetes has been widely recognized as a clinical entity since 1984. Most of the early clinical studies focused on African American or Afro-Caribbean individuals. It is now being recognized as an important clinical entity in sub-Saharan Africans, Asian and Indian populations, and Hispanic populations. Major questions remain as to its pathogenesis and whether it is a unique type of diabetes or a subset of more severe type 2 diabetes with greater loss of insulin action in target tissues. This review summarizes the main clinical and mechanistic studies to improve the understanding of ketosis-prone (Flatbush) diabetes. Recent Findings Little data are available on the magnitude of KPD in the different susceptible populations. It is relatively common in black populations. KPD is defined as a syndrome in which diabetes commences with ketoacidosis in individuals who are GAD and anti-islet cell antibody negative and have no known precipitating causes. The patients present during middle age, are overweight or mildly obese, and in many reports are more likely to be male. After intensive initial insulin therapy, many patients become insulin independent and can be well controlled on diet alone or diet plus oral medications. Summary The clinical course of KPD is like that of patients with type 2 diabetes rather than that of type 1 diabetes. Little differences are found in the clinical characteristics and clinical outcomes between patients presenting with KPD and those presenting with severe hyperglycemia with no ketoacidosis. The mechanisms responsible for the development of ketosis-prone diabetes as well its remission remain unknown.

While there has been a growing utilization of total pancreatectomy with islet autotransplantation (TPIAT) for patients with medically refractory chronic pancreatitis over the past few decades, there remains a lack of consensus clinical guidelines to inform the counseling and management of patients undergoing TPIAT. In this article, we review the current clinical practice and published experience of several TPIAT centers, outline key aspects in managing patients undergoing TPIAT, and discuss the glycemic outcomes of this procedure. Aiming for lower inpatient glucose targets immediately after surgery (usually 100–120 mg/dl), maintaining all patients on subcutaneous insulin for at least 3 months to “rest” islets before an attempt is made to wean insulin, and close outpatient endocrinology follow-up after TPIAT particularly in the first year is common and related to better outcomes. Although TPIAT procedures and glycemic outcomes may differ across surgical centers, overall, approximately one third of patients are insulin independent at 1 year after TPIAT. Higher islet yield and lower preoperative glucose levels are among the strongest predictors of short-term post-operative insulin independence. Beyond 1 year post-operatively, the clinical management and long-term glycemic outcomes of patients after TPIAT are more variable. A multidisciplinary approach is essential in optimizing the preoperative, inpatient, and post-operative management and counseling of patients about the expected glycemic outcomes after surgery. Consensus guidelines for the clinical management of diabetes after TPIAT and harmonization of data collection protocols among TPIAT centers are needed to address the current knowledge gaps in clinical care and research and to optimize glycemic outcomes after TPIAT.

Die funktionellen Ergebnisse der Insel(zell)-Transplantation haben sich kontinuierlich verbessert. Eine mogliche Indikation zur Transplantation besteht bei Patienten mit Typ-1-Diabetes (ohne signifikante Insulin-Restsekretion) mit Hypoglykamiesyndrom bzw. schwerst einstellbarem Diabetes (Brittle-Diabetes) oder mit terminaler Niereninsuffizienz und geplanter simultaner Nierentransplantation bzw. bereits vorangegangener Nierentransplantation. Durch eine Insel(zell)-Transplantation kann das primare Therapieziel einer guten und stabilen Stoffwechseleinstellung unter Vermeidung schwerer Hypoglykamien in der Mehrzahl der Falle erreicht werden. Nach Registerdaten betragt das Insel(zell)-Transplantatuberleben ein Jahr nach Transplantation 82%, nach 3 Jahren 75% und die Insulinunabhangigkeitsraten zum Einjahreszeitpunkt 43–50%, nach 3 Jahren 35%. Damit einher geht eine signifikante Verbesserung der Lebensqualitat und eine gegenuber alleiniger intensivierter Insulintherapie starkere Progressionshemmung diabetischer Folgekomplikationen. Patienten mit einem Typ-1-Diabetes mit Transplantationsindikation sollten eine Insel(zell)- oder Pankreastransplantation angeboten und dabei die Vor- und Nachteile beider Therapieverfahren sorgfaltig individuell abgewogen werden.

More than 500 patients with type 1 diabetes mellitus have now received islet transplants at over 50 institutions worldwide in the past 5 years. Rates of insulin independence at 1 year with current protocols are impressive. However, inexorable decay of islet function over time indicates that there are many opportunities for improvement. Improved control of glycosylated hemoglobin and reduced risk of recurrent hypoglycemia are seen as important benefits of islet transplantation, irrespective of the status regarding insulin independence. For the use of islet transplantation to expand it is essential that the donor-to-recipient ratio be reliably reduced to 1 : 1. Enormous opportunities lie ahead for the development of successful living donor islet transplantation, single donor protocols, improved engraftment, islet proliferation in vitro and in the recipient, alternative islet sources, and novel tolerizing drugs. With these emerging opportunities, islet transplantation may expand to include more patients with type 1 diabetes, including children, and will not be restricted to the most unstable forms of the disease, as it is today.

Islet transplantation as a procedure to induce insulin independence is still a long way from benefitting the population of more than I million type I diabetic patients in the United States. In addition to the problems involved with immune suppression, the most significant obstacle is a scarcity of human organs for transplantation. In 1999, only 5882 donated pancreases were available, of which only 50% could be expected to produce islet yields suitable for clinical purposes. In this article, we review various sources with the potential to provide tissue for transplantation. These sources include islet and nonislet cells derived from both human and nonhuman sources, with an emphasis on human cells.

Uremic diabetics have better survival rates with a kidney transplant than on dialysis. Adding a pancreas graft induces insulin independence and if the graft survives for >1 year, risk-adjusted registry analyses show improved patient and graft survival. Overall, however, as survival is similar for kidney–pancreas and kidney transplants alone from deceased pancreas donors, many questions remain.