Residual beta-cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty

Bonfanti, Riccardo; Bognetti, E.; Meschi, Franco; Brunelli, A; Riva, Maria Giorgia; Pastore, M. R.; Calori, Giliola; Chiumello, G

doi:10.1007/s005920050110

Cited by 48 publications

(58 citation statements)

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“…T1DM patients have an estimated 80 -90% loss in ␤ cell mass at diagnosis, although functioning mass still remains (6). Upon initiation of insulin therapy, 25-100% of newly diagnosed patients experience a transient restoration of remaining ␤ cell function, termed the "honeymoon period", that lasts from months to years (7)(8)(9)(10). This immunologically active time is clinically significant because it offers: 1) a window for potential therapeutic intervention aimed at arresting ␤ cell destruction, thus preserving endogenous ␤ cell mass and insulin secretion; and 2) a time to potentially measure processes related to ␤ cell destruction.…”

Section: T Ype 1 Diabetes Mellitus (T1dm)mentioning

confidence: 99%

Identification of a Molecular Signature in Human Type 1 Diabetes Mellitus Using Serum and Functional Genomics

Wang

Song

Geoffrey

et al. 2008

The Journal of Immunology

104

156

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Understanding active proinflammatory mechanisms at and before type 1 diabetes mellitus (T1DM) onset is hindered in humans, given that the relevant tissues are inaccessible and pancreatic immune responses are difficult to measure in the periphery by traditional approaches. Therefore, we investigated the use of a sensitive and comprehensive genomics strategy to investigate the presence of proinflammatory factors in serum. The sera of recent onset diabetes patients (n = 15, 12 possessing and 3 lacking islet cell autoantibodies), long-standing diabetes patients (n = 12), “at risk” siblings of diabetes patients (n = 9), and healthy controls (n = 12) were used to induce gene expression in unrelated, healthy PBMC. After culture, gene expression was measured with microarrays and normalized expression data were subjected to hierarchical clustering and multidimensional scaling. All recent onset sera induced an expression signature (192 UniGenes; fold change: >1.5, p < 0.01; false discovery rate: <0.01) that included IL-1 cytokine family members and chemokines involved in monocyte/macrophage and neutrophil chemotaxis, as well as numerous receptors and signaling molecules. This molecular signature was not induced with the sera of healthy controls or long standing diabetes patients, where longitudinal analysis of “at risk” siblings (n = 3) before and after onset support the hypothesis that the signature emerges years before onset. This study supports prior investigations of serum that reflect disease processes associated with progression to T1DM. Identification of unique inflammatory mediators may improve disease prediction beyond current islet autoantibodies. Furthermore, proinflammatory serum markers may be used as inclusion criteria or endpoint measures in clinical trials aimed at preventing T1DM.

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Section: T Ype 1 Diabetes Mellitus (T1dm)mentioning

confidence: 99%

Identification of a Molecular Signature in Human Type 1 Diabetes Mellitus Using Serum and Functional Genomics

Wang

Song

Geoffrey

et al. 2008

The Journal of Immunology

104

156

View full text Add to dashboard Cite

show abstract

“…In the extreme such as in type 1 diabetes, autoimmunemediated cell destruction is greater than the rate of regeneration leading to hyperglycaemia and invariably requiring insulin therapy. However, in rare cases, spontaneous remission characterized by increased C-peptide secretion has been reported in type 1 diabetic patients, clearly indicating the capacity of b-cell regeneration to prevail over autoimmune annihilation (Bonfanti et al 1998). Fundamental mechanisms governing b-cell replenishment remain to be identified.…”

mentioning

confidence: 99%

A focus on the role of Pax4 in mature pancreatic islet β-cell expansion and survival in health and disease

Brun¹,

Gauthier

2007

Journal of Molecular Endocrinology

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Blood glucose homeostasis is achieved by the regulation of insulin and glucagon secretion from the pancreatic islet b-and a-cells. Diabetes mellitus, which comprises a heterogeneous group of hyperglycaemic disorders, results mainly from inadequate mass and function of islet b-cells. Autoimmune destruction of b-cells causes type 1 diabetes, while type 2 is characterized by impaired insulin secretion and is often associated with diminished insulin action on its target tissues. Interestingly, similar to type 1 diabetes, a gradual loss of b-cell mass is observed in type 2 diabetes often requiring insulin therapy. Understanding the molecular mechanism that governs b-cell mass plasticity may provide a means to develop strategies to countera,ct b-cell death while increasing replication. Of particular interest is the islet-specific transcription factor paired box4 (Pax4) that was previously shown to be indispensable for the establishment of the b-cell lineage during development. However, recent accumulating evidence now suggest that Pax4 is also crucial for mature b-cell expansion and survival in response to physiological cues and that mutations or polymorphisms are associated with both type 1 and type 2 diabetes. In contrast, aberrant expression of Pax4 confers protection against apoptosis to insulinomas, whereas it promotes cell growth in lymphocytes. This review summarizes promising new published results supporting the important function of Pax4 in mature islet b-cell physiology and its contribution to pathophysiology when deregulated.

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“…Hence, measurement of insulin in the peripheral blood does not accurately reflect endogenous insulin secretion. Most studies have approximated insulin secretion with C-peptide levels measured when fasting, at random, or following provocation with mixed meals or glucagon (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). While glucagon produces a reliable insulin response, it does not simulate normal physiology while a mixed meal is physiological.…”

mentioning

confidence: 99%

Insulin Secretion in Type 1 Diabetes

et al. 2004

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Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing ␤-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of ␤-cell function at an average rate of 756 ؎ 132 pmol/month to a final value of 28 ؎ 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA 1c (P ‫؍‬ 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction. Diabetes 53: 426 -433, 2004

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Residual beta-cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty

Cited by 48 publications

References 0 publications

Identification of a Molecular Signature in Human Type 1 Diabetes Mellitus Using Serum and Functional Genomics

Identification of a Molecular Signature in Human Type 1 Diabetes Mellitus Using Serum and Functional Genomics

A focus on the role of Pax4 in mature pancreatic islet β-cell expansion and survival in health and disease

Insulin Secretion in Type 1 Diabetes

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