Distinct Changes in Serum Fibroblast Growth Factor 21 Levels in Different Subtypes of Diabetes

Xiao, Yang; Xu, Aimin; Law, Lawrence Siu-Chun; Chen, Cheng; Li, Hui; Li, Xia; Yang, Lin; Liu, Shiping; Zhou, Zhiguang; Lam, Karen S.L.

doi:10.1210/jc.2011-1930

Cited by 95 publications

(98 citation statements)

References 20 publications

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“…A total of 25 adults with type 2 diabetes diagnosed within 1 year and 25 age-and sex-matched healthy control subjects were recruited at the Diabetes Center, Second Xiangya Hospital of Central South University, and the inclusion criteria were described in our previous study (22).…”

Section: Study Cohortmentioning

confidence: 99%

“…Serum levels of C-peptide and C-reactive protein were quantified using a chemiluminescence immunoassay on a Bayer 180SE Automated Chemiluminescence System (Bayer AG, Leverkusen, Germany) and an immunoturbidimetric assay (Orion Diagnostica, Espoo, Finland), respectively. The titers of GADA, IA2A, and ZnT8A were determined by in-house radioligand assays, as previously described (22,23).…”

Section: Clinical and Biochemical Assessmentsmentioning

confidence: 99%

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Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

et al. 2014

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Type 1 diabetes (T1D) is an autoimmune disease resulting from the self-destruction of insulin-producing β-cells. Reduced neutrophil counts have been observed in patients with T1D. However, the pathological roles of neutrophils in the development of T1D remain unknown. Here we show that circulating protein levels and enzymatic activities of neutrophil elastase (NE) and proteinase 3 (PR3), both of which are neutrophil serine proteases stored in neutrophil primary granules, were markedly elevated in patients with T1D, especially those with disease duration of less than 1 year. Furthermore, circulating NE and PR3 levels increased progressively with the increase of the positive numbers and titers of the autoantibodies against β-cell antigens. An obvious elevation of NE and PR3 was detected even in those autoantibody-negative patients. Increased NE and PR3 in T1D patients are closely associated with elevated formation of neutrophil extracellular traps. By contrast, the circulating levels of α1-antitrypsin, an endogenous inhibitor of neutrophil serine proteases, are decreased in T1D patients. These findings support an early role of neutrophil activation and augmented neutrophil serine proteases activities in the pathogenesis of β-cell autoimmunity and also suggest that circulating NE and PR3 may serve as sensitive biomarkers for the diagnosis of T1D.

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Section: Study Cohortmentioning

confidence: 99%

Section: Clinical and Biochemical Assessmentsmentioning

confidence: 99%

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

et al. 2014

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“…Although a previously published Chinese study [16] showed a decreased basal FGF-21 in T1DM, the basal serum FGF-21 concentration in long standing T1DM patients without residual pancreatic β-cell function has not been studied so far.…”

Section: Introductionmentioning

confidence: 95%

“…So far, only one study explored basal serum FGF-21concentration in newly diagnosed T1DM patients, describing markedly lower FGF-21 in comparison with healthy population, T2DM and latent autoimmune diabetes in adults [16]. The authors proposed that the autoimmune process destroys pancreatic β-cells and consequently reduces FGF-21 secretion in T1DM.…”

Section: Introductionmentioning

confidence: 99%

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

et al. 2014

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“…Actually, blood and CSF lactate and pyruvate levels also changed following her glycemic control in our case (Table 2). Moreover, a study showed the significantly lower level of FGF21 in patients with type 1 diabetes, which was likely to show reduced insulin secretions and non-obesity, than ones with type 2 diabetes (Xiao et al 2012). Taken together with reduced insulin secretions and without obesity in our case, the substantially high FGF21 concentrations on admission might come from hyperglycemia-induced mitochondrial dysfunctions.…”

Section: Discussionmentioning

confidence: 47%

Successful Glycemic Control Decreases the Elevated Serum FGF21 Level without Affecting Normal Serum GDF15 Levels in a Patient with Mitochondrial Diabetes

Murakami

Ueba

Shinoto

et al. 2016

Tohoku J. Exp. Med.

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Mitochondrial diabetes mellitus is a subtype of diabetes linked to mutations in mitochondrial DNA. In patients with mitochondrial diabetes mellitus, the effect of glycemic control on the serum concentrations of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) has not been evaluated. FGF21 and GDF15 have been reported to be useful biomarkers for the diagnosis and severity assessment of mitochondrial diseases like mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recent studies have shown FGF21 acts in an endocrine fashion to regulate glucose and lipid metabolism in type 2 diabetes mellitus, while the exact biological functions of GDF15 remain unknown. Although mitochondrial diabetes mellitus is commonly found in cases with mitochondrial diseases, the comparison of FGF21 and GDF15 levels between those with and without diabetes has not been performed. Here, we report a 24-year-old woman with mitochondrial diabetes mellitus, who showed a high level of serum FGF21, but not serum GDF15, at diagnosis. In our case, liraglutide, a glucagon-like peptide-1 receptor agonist, added to insulin glargine was effective for her glycemic control and showed no adverse effects, including gastrointestinal symptoms and hypoglycemia, during a 14-week observation. The successful glycemic control caused a decrease in the FGF21 level, without affecting the GDF15 level. Thus, we should consider patients' glycemic control levels in using FGF21 values for the diagnosis of mitochondrial diseases. In addition, sustained GDF15 levels during glycemic treatment in our case suggest the usefulness of GDF15 as a marker for clinical severity of muscle-manifested mitochondrial diseases.

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Distinct Changes in Serum Fibroblast Growth Factor 21 Levels in Different Subtypes of Diabetes

Abstract: Serum FGF21 level is increased in type 2 diabetes but decreased in type 1 diabetes and LADA. In autoimmune diabetes, the reduction in circulating FGF21 is closely associated with markers of pancreatic β-cell autoimmunity.

Cited by 95 publications

References 20 publications

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

Increased Neutrophil Elastase and Proteinase 3 and Augmented NETosis Are Closely Associated With β-Cell Autoimmunity in Patients With Type 1 Diabetes

Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls

Successful Glycemic Control Decreases the Elevated Serum FGF21 Level without Affecting Normal Serum GDF15 Levels in a Patient with Mitochondrial Diabetes

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