Journal ArticleDOI
Pancreatic beta-cell mass in European subjects with type 2 diabetes.
TLDR
The average β‐cell mass is about 39% lower in T2D subjects compared with matched controls, and its decrease with duration of the disease could be a consequence of diabetes that, with further impairment of insulin secretion, contributes to the progressive deterioration of glucose homeostasis.Abstract:
Decreases in both beta-cell function and number can contribute to insulin deficiency in type 2 diabetes. Here, we quantified the beta-cell mass in pancreas obtained at autopsy of 57 type 2 diabetic (T2D) and 52 non-diabetic subjects of European origin. Sections from the body and tail were immunostained for insulin. The beta-cell mass was calculated from the volume density of beta-cells (measured by point-counting methods) and the weight of the pancreas. The pancreatic insulin concentration was measured in some of the subjects. beta-cell mass increased only slightly with body mass index (BMI). After matching for BMI, the beta-cell mass was 41% (BMI 15 years of overt diabetes respectively). Pancreatic insulin concentration was 30% lower in patients. In conclusion, the average beta-cell mass is about 39% lower in T2D subjects compared with matched controls. Its decrease with duration of the disease could be a consequence of diabetes that, with further impairment of insulin secretion, contributes to the progressive deterioration of glucose homeostasis. We do not believe that the small difference in beta-cell mass observed within 5 years of onset could cause diabetes in the absence of beta-cell dysfunction.read more
Citations
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Journal ArticleDOI
Type 2 diabetes mellitus.
Ralph A. DeFronzo,Ele Ferrannini,Leif Groop,Robert R. Henry,William H. Herman,Jens J. Holst,Frank B. Hu,C. Ronald Kahn,Itamar Raz,Gerald I. Shulman,Donald C. Simonson,Marcia A. Testa,Ram Weiss +12 more
TL;DR: The greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications.
Journal ArticleDOI
Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
TL;DR: More effective therapies to slow progressive loss of β-cell function are needed and additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.
Journal ArticleDOI
Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure
TL;DR: It is proposed that dedifferentiation trumps endocrine cell death in the natural history of β cell failure and suggested that treatment ofβ cell dysfunction should restore differentiation, rather than promoting β cell replication.
Journal ArticleDOI
Type 2 diabetes across generations: from pathophysiology to prevention and management
TL;DR: Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena, and maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies.
Journal ArticleDOI
Diabetes Mellitus and the β Cell: The Last Ten Years
TL;DR: What ails the β cell and how its function may be restored is reviewed here, with environmental and lifestyle factors, via obesity, accounting for the current dramatic increase in T2DM.
References
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Journal ArticleDOI
β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes
Alexandra E. Butler,Juliette Janson,Susan Bonner-Weir,Robert A. Ritzel,Robert A. Rizza,Peter C. Butler +5 more
TL;DR: Since the major defect leading to a decrease in β-cell mass in type 2 diabetes is increased apoptosis, while new islet formation andβ-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 Diabetes.
Journal ArticleDOI
The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes.
TL;DR: Greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 1 diabetes.
Journal Article
U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease
R. C. Turner,Carole A. Cull,Irene M Stratton,Susan E. Manley,E. M. Kohner,David R Matthews,Neil Haw.,Jonathan C. Levy,Rury R. Holman +8 more
TL;DR: Sulfonylurea, metformin, and insulin therapies were similarly effective in improving glucose control compared with a policy of diet therapy and whether any specific therapy is advantageous or disadvantageous.
Journal ArticleDOI
Pathologic Anatomy of the Pancreas in Juvenile Diabetes Mellitus
TL;DR: Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease, and may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on theinsular tissue.
Journal ArticleDOI
The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
Over Cabrera,Dora M. Berman,Norma S. Kenyon,Camillo Ricordi,Per Olof Berggren,Per Olof Berggren,Aiejandro Caicedo +6 more
TL;DR: It is concluded that the unique cellular arrangement of human islets has functional implications for islet cell function.