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

Abstract

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.

Circulating Cardiac Biomarkers in Diabetes Mellitus: A New Dawn for Risk Stratification—A Narrative Review

“…Serum levels of GDF15 were found to be higher in prediabetes/T2DM patients than in healthy volunteers and independently associated with CV risk scores [124], body mass index, waist-to-hip ratio [125], insulin resistance [126], hs-CRP [127] and parameters of glucose metabolism (C-peptide, fasting pre-hepatic beta cell function, impaired fasting glucose) [128,129], while successful glycemic control did not cause a decrease in GDF15 levels [130].…”

Association of growth-differentiation factor-15 with the number of circulating proangiogenic endothelial progenitor cells in patients with type 2 diabetes mellitus

“…However, there are severe controversies in this issue, because few reports in opposite revealed that lowered GDF-15 levels are beneficial against endothelial injury and microvascular inflammation [35,36]. In contrast, there is evidence that successful glycemic control and treatment of dyslipidemia with statins in moderate-to-high doses did not cause changes in plasma levels of GDF-15 [37,38]. Although traditionally achieving of full control for hyperglycemia and hyperlipidemia is considered a predictor of better clinical outcomes in people with diabetes, lack of GDF-15 dynamic requires to be clarified.…”

Regulation of diurnal energy balance by mitokines

“…Both are considered as mitokines induced in response to mitochondrial but also ER stress and other cellular stress situations in various organs and tissue; and both have been demonstrated to exert systemic metabolic effects [12,14,45]. FGF21 and GDF15 are used as biomarkers for the diagnosis and severity assessment of mitochondrial diseases including mitochondrial myopathy, [46,47], but they were also shown to be elevated in patients with different inherited metabolic diseases that are not restricted to mitochondrial disorders [48]. Interestingly, circulating FGF21 and in particular GDF15 increase with aging, and both have been suggested as markers of biological age in humans [49].…”