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  • 1
    Online Resource
    Online Resource
    Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-5-12)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-5-12)
    Abstract: Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D). Study design and methods Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention. Results Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both. Conclusions Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients. Clinical trial registration https://drks.de/search/en/trial/DRKS00014287 , identifier DRKS00014287.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2023.1143799
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 2
    Online Resource
    Online Resource
    Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study
    The Endocrine Society ; 2022
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 107, No. 8 ( 2022-07-14), p. 2167-2181
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 8 ( 2022-07-14), p. 2167-2181
    Abstract: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome. Objective Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways. Design/Participants Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up. Main Outcomes Measures Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints. Results FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [−30.3 (−35.7, −24.9) mg/g; P ≤ 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23] . FMD reduced HOMA-IR [−3.8 (−5.6, −2.0); P ≤ 0.05] and soluble urokinase plasminogen activator receptor [−156.6 (−172.9, −140.4) pg/mL; P ≤ 0.05] , while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [−1.9 (−3.7, −0.1), P ≤ 0.05]) was sustained. Conclusions Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgac197
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 3
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    Online Resource
    Sciatic nerve fractional anisotropy and neurofilament light chain protein are related to sensorimotor deficit of the upper and lower limbs in patients with type 2 diabetes
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-3-14)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-14)
    Abstract: Diabetic sensorimotor polyneuropathy (DSPN) is one of the most prevalent and poorly understood diabetic microvascular complications. Recent studies have found that fractional anisotropy (FA), a marker for microstructural nerve integrity, is a sensitive parameter for the structural and functional nerve damage in DSPN. The aim of this study was to investigate the significance of proximal sciatic nerve’s FA on different distal nerve fiber deficits of the upper and lower limbs and its correlation with the neuroaxonal biomarker, neurofilament light chain protein (NfL). Materials and methods Sixty-nine patients with type 2 diabetes (T2DM) and 30 healthy controls underwent detailed clinical and electrophysiological assessments, complete quantitative sensory testing (QST), and diffusion-weighted magnetic resonance neurography of the sciatic nerve. NfL was measured in the serum of healthy controls and patients with T2DM. Multivariate models were used to adjust for confounders of microvascular damage. Results Patients with DSPN showed a 17% lower sciatic microstructural integrity compared to healthy controls ( p & lt;0.001). FA correlated with tibial and peroneal motor nerve conduction velocity (NCV) (r=0.6; p & lt;0.001 and r=0.6; p & lt;0.001) and sural sensory NCV (r=0.50; p & lt;0.001). Participants with reduced sciatic nerve´s FA showed a loss of function of mechanical and thermal sensation of upper (r=0.3; p & lt;0.01 and r=0.3; p & lt;0.01) and lower (r=0.5; p & lt;0.001 and r=0.3; p = & lt;0.01) limbs and reduced functional performance of upper limbs (Purdue Pegboard Test for dominant hand; r=0.4; p & lt;0.001). Increased levels of NfL and urinary albumin-creatinine ratio (ACR) were associated with loss of sciatic nerve´s FA (r=-0.5; p & lt;0.001 and r= -0.3, p = 0.001). Of note, there was no correlation between sciatic FA and neuropathic symptoms or pain. Conclusion This is the first study showing that microstructural nerve integrity is associated with damage of different nerve fiber types and a neuroaxonal biomarker in DSPN. Furthermore, these findings show that proximal nerve damage is related to distal nerve function even before clinical symptoms occur. The microstructure of the proximal sciatic nerve and is also associated with functional nerve fiber deficits of the upper and lower limbs, suggesting that diabetic neuropathy involves structural changes of peripheral nerves of upper limbs too.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2023.1046690
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 4
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    Online Resource
    Elevated Markers of DNA-Damage and Senescence are Associated with the Progression for Albuminuria and Restrictive Lung Disease in Patients with Type 2 Diabetes
    Elsevier BV ; 2022
    In:  SSRN Electronic Journal
    Details
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    URL: Article
    DOI: 10.2139/ssrn.4175217
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
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  • 5
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    Online Resource
    Correction to: Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy
    Springer Science and Business Media LLC ; 2022
    In:  Diabetologia Vol. 65, No. 1 ( 2022-01), p. 257-257
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 65, No. 1 ( 2022-01), p. 257-257
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-021-05588-z
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1458993-X
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  • 6
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    Online Resource
    Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy
    Springer Science and Business Media LLC ; 2021
    In:  Diabetologia Vol. 64, No. 12 ( 2021-12), p. 2843-2855
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 64, No. 12 ( 2021-12), p. 2843-2855
    Abstract: The individual risk of progression of diabetic peripheral neuropathy is difficult to predict for each individual. Mutations in proteins that are responsible for the process of myelination are known to cause neurodegeneration and display alteration in experimental models of diabetic neuropathy. In a prospective observational human pilot study, we investigated myelin-specific circulating mRNA targets, which have been identified in vitro, for their capacity in the diagnosis and prediction of diabetic neuropathy. The most promising candidate was tested against the recently established biomarker of neural damage, neurofilament light chain protein. Methods Schwann cells were cultured under high-glucose conditions and mRNAs of various myelin-specific genes were screened intra- and extracellularly. Ninety-two participants with type 2 diabetes and 30 control participants were enrolled and evaluated for peripheral neuropathy using neuropathy deficit scores, neuropathy symptom scores and nerve conduction studies as well as quantitative sensory testing at baseline and after 12/24 months of a follow-up period. Magnetic resonance neurography of the sciatic nerve was performed in 37 individuals. Neurofilament light chain protein and four myelin-specific mRNA transcripts derived from in vitro screenings were measured in the serum of all participants. The results were tested for associations with specific neuropathic deficits, fractional anisotropy and the progression of neuropathic deficits at baseline and after 12 and 24 months. Results In neuronal Schwann cells and human nerve sections, myelin protein zero was identified as the strongest candidate for a biomarker study. Circulating mRNA of myelin protein zero was decreased significantly in participants with diabetic neuropathy ( p   〈  0.001), whereas neurofilament light chain protein showed increased levels in participants with diabetic neuropathy ( p   〈  0.05). Both variables were linked to altered electrophysiology, fractional anisotropy and quantitative sensory testing. In a receiver-operating characteristic curve analysis myelin protein zero improved the diagnostic performance significantly in combination with a standard model (diabetes duration, age, BMI, HbA 1c ) from an AUC of 0.681 to 0.836 for the detection of diabetic peripheral neuropathy. A follow-up study revealed that increased neurofilament light chain was associated with the development of a hyperalgesic phenotype ( p   〈  0.05), whereas decreased myelin protein zero predicted hypoalgesia ( p   〈  0.001) and progressive loss of nerve function 24 months in advance (HR of 6.519). Conclusions/interpretation This study introduces a dynamic and non-invasive assessment strategy for the underlying pathogenesis of diabetic peripheral neuropathy. The diagnosis of axonal degeneration, associated with hyperalgesia, and demyelination, linked to hypoalgesia, could benefit from the usage of neurofilament light chain protein and circulating mRNA of myelin protein zero as potential biomarkers. Graphical abstract
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s00125-021-05557-6
    RVK:
    XA 40615
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 7
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    Online Resource
    Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 10 ( 2023-09-18), p. e979-e988
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 10 ( 2023-09-18), p. e979-e988
    Abstract: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. Methods A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as “healthy” and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. Results Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P & lt; .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P & lt; .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, “sensory loss” was most strongly associated with PN development (adjusted HR, 4.35; P = .011). Conclusion We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgad248
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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  • 8
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    Online Resource
    Phase angle of bioelectrical impedance analysis as an indicator for diabetic polyneuropathy in type 2 diabetes mellitus
    The Endocrine Society ; 2024
    In:  The Journal of Clinical Endocrinology & Metabolism ( 2024-01-12)
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, ( 2024-01-12)
    Abstract: Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routine leading to increased morbidity and mortality. Objective We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory and physical markers of DPN to evaluate PhA as possible diagnostic method for DPN. Materials and methods In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), amongst which 63 had DPN. The PhA was calculated from multi-frequency BIA. Nerve conduction studies (NCS), quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography (MRN) to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed. Results T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, p = 0.007, + 6.1%) and healthy controls (6.18 ± 0.08, p & lt; 0.001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=0.28; β=0.31, p & lt; 0.001) and tibial nerves (β=0.28; β=0.32, p & lt; 0.001), Z-scores of QST (thermal detection β=0.30, p & lt; 0.05) and the FA (β=0.60, p & lt; 0.001). ROC analysis showed similar performance of PhA in comparison to mentioned diagnostic methods. Conclusion The study shows that PhA is in comparison to other test systems used, at least an equally good and much easier to handle, investigator independent marker for detection of DPN.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgad737
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2024
    detail.hit.zdb_id: 2026217-6
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