Histological analysis of donor pancreases coupled with measurement of serum C-peptide in medical cohorts has challenged the theory that beta cells are eventually damaged in type 1 diabetes. that proof for fresh beta cell development in humans a long time from diagnosis is bound, and that development may be very minimal if present. We review latest contributions towards the controversy around beta cell abnormalities adding to the pathogenesis of type 1 diabetes. We discuss proof for repair of beta cell function also, instead of mass, in recent-onset type 1 diabetes, but focus on the lack of data assisting practical recovery in the establishing of long-duration diabetes. Finally, potential areas of study are suggested to greatly help resolve the foundation and phenotype of residual beta cells that persist in a few, however, Ostarine inhibitor database not all, people who have type 1 diabetes. = 41 diabetic donors:= 26= 15RO: 14.3 7.558 T1D donors:= 18= 40RO: 11.5 9.0= 26 T1D donors,= 13= 5= 8= 45 nondiabetic control donors0: 23 11= 42 T1D donors= 14 nondiabetic control donorsND4C67 yearsbBeta cells identified in 88% of donors with T1D.vs 1.140 0.90%; p< 0.0001).9 T1D donors, all RO= 9 nondiabetic control donors23.44 10.24336.8416.2 times90% mean decrease in beta cell mass in T1D vs control (array: 70C99%).= 9 donors, through the Joslin Medalist Research10.0 9.764.3 9.9 years9/9 pancreases got some residual insulin+ cells.= 2 (age group of onset 23 and 30), insulin+ cells were more prevalent and located clearly within islets. In one of these donors, insulin+ cells were distributed in a lobular pattern.Lam et al (2017) USA= 47 T1D donors, from9= 38= 59 non-diabetic control donorsRO: 14.1 7.0= 128 T1D donors, from EADB = 133 T1D donors, from nPODEADB: 11 (5C16)d= 20)= 14)= 16).32)= 31)= 49). Open in a separate window aCategory 0, ICIs throughout the pancreas; category 1+, ICIs in one lobule; GTF2H category 2+, ICIs in >1 lobule bRange cSummary statistics provided for cases from the Exeter Archival Diabetes Biobank and nPOD biorepositories; possible overlap with data shown in Lam et al (2007) , which reported on a subset of nPOD donors dMedian (interquartile range) EADB, Exeter Archival Diabetes Biobank; Insulin+, insulin-positive; LD, long-duration type 1 diabetes (duration >3 years); ND, no data; RO, recent-onset type 1 diabetes (duration 3 years); T1D, type 1 diabetes A number of themes are evident from the published literature. First, beta cell mass is markedly heterogeneous in people Ostarine inhibitor database with type 1 diabetes and even amongst those without diabetes [24C27]. Beta cell mass at type 1 diabetes onset varies and may not match severity of clinical presentation [10,25,28]. In longstanding type 1 diabetes, beta cells can be observed in a significant proportion of donors, but overall beta cell mass is markedly reduced [1, 9, 11C13, 22, 23]. For example, a recent analysis of 47 nPOD donors with a disease duration ranging from 0 to 41 years found that 67% of donors had demonstrable ICIs. However, even in those with remaining ICIs, total beta cell mass was reduced by an estimated 88C95% . Consistent with serum C-peptide analyses, there is data to suggest that ICIs are more likely to be observed in donors with an older age of diagnosis . Other analyses describe a decline in beta cell area and mass with increasing disease duration . Insulitis is common in individuals with disease duration <1 year, but immune infiltrates are not present in all islets within an affected individual . In long-duration type 1 diabetes, insulitis may still be observed Ostarine inhibitor database but is much rarer . The progressive decline in beta cell function after type 1 diabetes diagnosis is described in numerous longitudinal studies of Ostarine inhibitor database serum C-peptide post-diagnosis. Initial decline of beta cell function seems to follow a loglinear trajectory [30C34], with age of diagnosis significantly affecting C-peptide level at the time of diagnosis but maybe having less effect on gradient of decrease.