Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Greco, Carla; Nascimbeni, Fabio; Carubbi, Francesca; Andreone, Pietro; Simoni, Manuela; Santi, Daniele

doi:10.3390/jcm10194466

Cited by 8 publications

(7 citation statements)

References 59 publications

(72 reference statements)

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“…At variance with those studies [ 22 , 24 ], however, we found no association between FLI and DR or DSP. Therefore, our findings are more in line with those of a recent meta-analysis showing increased DSP prevalence in subjects with type 2 diabetes with NAFLD, but not in those with type 1 diabetes [ 25 ].…”

Section: Discussionsupporting

confidence: 92%

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study

Garofolo,

Lucchesi,

Giambalvo

et al. 2024

Cardiovasc Diabetol

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Background Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. Methods We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. Results Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30–59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30–59 (HR 2.85, 95% CI 1.49–5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27–11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78–2.97) for FLI 30–59 and 3.04 (1.59–5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30–59: HR 1.24, 0.62–2.48; FLI ≥ 60: 2.54, 1.30–4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65–6.34, p = 0.001) for FLI 30–59 and 5.41 (2.70–10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. Conclusions This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

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Section: Discussionsupporting

confidence: 92%

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study

Garofolo,

Lucchesi,

Giambalvo

et al. 2024

Cardiovasc Diabetol

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“…[35][36][37] As a result, imaging modalities such as ultrasound are commonly used as a first-line diagnostic step in evaluating hepatic steatosis, owing to its safety, availability, and low cost. 38 According to Greco et al 39 it is evident that diabetic patients should have a hepatic ultrasonography examination to detect NAFLD early.…”

Section: Discussionmentioning

confidence: 99%

“…[45][46][47][48] Insulin resistance could also play a part in the development of peripheral neuropathy, explaining why it is so common in people with pre-diabetes 42 and why insulin sensitisers, such as metformin and thiazolidinediones, could decrease the occurrence of diabetic peripheral neuropathy compared to insulin or insulin secretagogues, after adjusting for differences in glycemic control. 47 A meta-analysis study by Greco et al 39 They showed that DPN prevalence was significantly higher in T2DM patients with NAFLD. This could be because of not limiting the NAFLD diagnosis method to ultrasonography, as they included studies using ultrasound, composite noninvasive biomarkers, or ultrasound elastography for NAFLD diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…24 It is believed that the severity of NAFLD may have a part in the development of comorbidities. 39 Liver biopsy is the gold standard method for detecting NAFLD severity in terms of steatosis quantity, necro-inflammation, and fibrosis, but it is not suited for large-scale screening because of invasiveness and expense. 10 Several new non-invasive approaches, such as composite biomarkers, ultrasound elastography, and magnetic resonance, have shown to be effective in determining the severity of NAFLD and have been advocated for broad usage in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of diabetic neuropathy in nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta-analysis

Mohammad Rahmanian,

Shirin Yaghoobpoor,

Deravi

et al. 2024

NeuroAsia

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Nonalcoholic fatty liver disease (NAFLD) refers to the uncontrolled accumulation of triglyceride (TG) in the liver when the person has no other liver disease etiologies. Among all causes of neuropathy, diabetic neuropathy is the most common one worldwide, and it causes notable morbidity and increases mortality. The prevalence of diabetic neuropathy and NAFLD has been demonstrated in few studies. This study aims to summarize existing data estimating peripheral diabetic neuropathy prevalence among sonographically detected NAFLD patients. We searched PubMed, Scopus, Web of Science, and Google scholar for articles in the English language up until October 2021 for the clinical trials of diabetic neuropathy in NAFLD patients and used the articles for a systematic review and meta-analysis. Seven studies (6,918 patients with type 2 diabetes mellitus (T2DM)) were involved. The prevalence of diabetic neuropathy among T2DM patients with ultrasound (US) detected-NAFLD was 0.48 (95% CI= 0.31-0.65, I2= 99.01%), however it was not significantly different from patients without NAFLD (OR=1.02, 95% CI= 0.89-1.17. p=0.748, I2=81.6%). The prevalence of diabetic neuropathy among T2DM patients with NAFLD is not significantly different from patients without NAFLD.

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“…Previous studies have shown a significantly increased prevalence of DPN in T2DM with Nonalcoholic Fatty Liver Disease (NAFLD). 31 This may be related to the fact that patients with NAFLD have enhanced pro-inflammatory and pro-atherosclerotic effects. Both ALB and FIB selected for this study are produced by the liver, and the combination of the two amplifies the inflammatory response in the body and is a more sensitive indicator of response to inflammation.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Fibrinogen/Albumin and Diabetic Peripheral Neuropathy

Ban,

Pan,

Yang

et al. 2023

DMSO

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Purpose This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN). Patients and Methods A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV). Results The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94±1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P<0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c. Conclusion The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.

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Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Cited by 8 publications

References 59 publications

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study

Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study

Prevalence of diabetic neuropathy in nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta-analysis

Correlation Between Fibrinogen/Albumin and Diabetic Peripheral Neuropathy

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