Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
by
, , ,
Julia Fischer
1,2,3,4,5,*,
Nina Judith Hos
2,3,6,
Sophie Tritschler
1,2,
Joel Schmitz-Peters
7,8,
Raja Ganesan
2,9,10,
Chiara Calabrese
2,9,
Petra Schiller
11,
Hannah Brunnert
1,9,
Angela Nowag
1,
Sandra Winter
1,4,
Ruth Hanßen
7,8,
Katja Römer
12,
Nazifa Qurishi
12,
Isabelle Suarèz
1,3,
Norma Jung
1,
Clara Lehmann
1,3,
Georg Plum
9,
Michael Faust
7,
Pia Hartmann
3,9,13 and
Nirmal Robinson
2,9,10 1
Department I of Internal Medicine, Division of Infectious Diseases, University Hospital of Cologne, 50936 Cologne, Germany
2
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50923 Cologne, Germany
3
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 38124 Cologne, Germany
4
Center for Molecular Medicine Cologne (CMMC), 50931 Cologne, Germany
5
Department B for Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, University Hospital of Münster, 48149 Münster, Germany
6
Department of Clinical Research, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
7
Policlinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, 50936 Cologne, Germany
8
Max-Planck Institute for Metabolism Research, 50931 Cologne, Germany
9
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50923 Cologne, Germany
10
Center for Cancer Biology, University of South Australia and SA Pathology, UniSA CRI Building, GPO Box 2471, Adelaide, SA 5001, Australia
11
Institute for Medical Statistics and Computational Biology, Medical Faculty and University Hospital of Cologne, University of Cologne, 50923 Cologne, Germany
12
Gemeinschaftspraxis Gotenring, 50679 Cologne, Germany
13
Department for Infectious Diseases, St. Vinzenz Hospital, 50733 Cologne, Germany
*
Author to whom correspondence should be addressed.
Diabetology 2025, 6(6), 45; https://doi.org/10.3390/diabetology6060045
Submission received: 24 November 2024
/
Revised: 8 April 2025
/
Accepted: 6 May 2025
/
Published: 23 May 2025
(This article belongs to the Special Issue Feature Papers in Diabetology 2024)
Abstract
:Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. Methods: Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. Results: We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients.
1. Introduction
The rising incidence of Type 2 diabetes mellitus (T2DM) and its complications pose a big threat to human health worldwide due to increased mortality [1]. The International Diabetes Federation (IDF) estimates that the number of affected patients will rise from 463 million in 2019 to 700 million in 2045 [2]. Thus, understanding T2DM pathogenesis in the context of risk factors such as aging is crucial for designing novel therapeutic strategies to prevent and treat T2DM.
Aging is a known risk factor for the development of insulin resistance, resulting in the development of T2DM [3,4]. A large number of T2DM cases can be attributed to sedentary lifestyle, reduced physical activity, and energy-dense diets, leading to obesity and T2DM, which makes it challenging to prevent and treat T2DM [4]. Age-dependent alterations in the immune system, such as immunosenescence, could contribute to a dampened immune response in diabetic patients, which makes them more susceptible to infections [5]. T2DM is also associated with increased levels of inflammation, indicating a dysregulated immune system [6,7]. Moreover, metabolic hormones causing diabetes and obesity, such as leptin, are known to regulate immune responses [8,9]. Accordingly, previous studies have shown elevated levels of acute-phase proteins such as C-reactive protein (CRP), as well as proinflammatory cytokines in the sera of T2DM patients [10,11,12], which were also predictive markers of T2DM [11,13,14]. These findings have led to the notion that T2DM is an inflammatory disease, which could be treated by targeting inflammatory pathways, for instance by using IL-1 receptor antagonists [15,16].
Sirtuin1 (SIRT1) is a NAD+-dependent deacetylase that regulates lifespan and metabolism. Previously, we have shown that SIRT1 critically regulates innate immune defense mechanisms, such as autophagy and inflammation, in response to bacterial infections [14]. During S. Typhimurium infection of macrophages, SIRT1 was required for deacetylation and subsequent activation of LKB1, which resulted in the transient activation of AMPK-mediated autophagy [17]. Thus, LKB1-AMPK regulates autophagy. Moreover, it has been shown that SIRT1 is downregulated by autophagy in senescence and aging [18].
SIRT1 has been shown to directly regulate autophagy by direct acetylation of autophagic proteins, such as ATG5, ATG7, and ATG8, and therefore has been recognized as a positive regulator of autophagy [19]. A recent study has shown that SIRT1 is degraded through autophagy during aging and senescence [18]. p62 is an autophagic adaptor, which is degraded along with autophagic cargo and is commonly used as a reporter of autophagy activity, but has also been shown to regulate inflammation and anti-oxidative stress responses by activating NF-κB and NRF2, respectively [20,21]. During autophagy, LC-3I is conjugated to LC-3 II, which is then recruited to the autophagosomal membranes [22]. Furthermore, autophagy is a potent anti-inflammatory process [23]. However, where SIRT1 expression is altered in immune cells from patients suffering from T2DM remains unclear. Therefore, we investigate the expression of SIRT1 and its correlation with autophagy in a cohort of T2DM patients in comparison to non-diabetic controls.
In this study, we found that an age-dependent decrease in SIRT1 expression in human PBMCs is more pronounced in diabetic patients. Correspondingly, we also observed reduced LC3-II/I levels in the selected study patients. Moreover, decreased levels of SIRT1 also correlated with reduced accumulation of p62.
2. Material and Methods
2.1. Study Design
Ethical approval for this study was granted by the ethics committee of the University Hospital of Cologne (File No.: 12-164, 16 August 2012) and the Ärztekammer Nordrhein (File No.: 2012421, approval date 5 February 2013). Between June 2012 and July 2013, 43 study participants with T2DM were recruited from the endocrinological outpatient department of the University Hospital Cologne and 57 study participants from the general medical practice of Cologne. Inclusion criteria were informed consent, age > 18 years, T2DM for at least one year, and under antidiabetic treatment or non-diabetic subjects. In the non-diabetic subjects, prediabetes was excluded by determination of fasting glucose at day of presentation and afterwards when showing elevated blood glucose levels for five subjects. Exclusion criteria for all study participants were any underlying chronic infections or autoimmune disease, intake of immunomodulatory drugs such as biologicals, and no obtained written consent.
2.2. PBMC Isolation
PBMCs were isolated from the blood of diabetic patients (n = 36) and non-diabetic controls (n = 62) by using Lymphoprep™ (Stem Cell) gradient separation according to the manufacturer’s guidelines. PBMCs were stored in liquid nitrogen until usage.
2.3. Western Blot
PBMCs were lysed in radioimmunoprecipitation assay (RIPA) buffer supplemented with 1x protease/phosphatase inhibitor mixture (Thermo Fisher Scientific, Waltham, MA, USA). Protein concentrations were estimated using Pierce BCA Protein Assay Kit (Thermo Fisher Scientific, Waltham, MA, USA), according to the manufacturer’s instructions. Equal amounts of protein were separated on 10% or 12% SDS/PAGE gels. The proteins were then transferred onto a polyvinylidene difluoride (PVDF) membrane and probed with the following antibodies: SIRT1 (#2496, Cell Signaling, Leiden, Netherlands), SQSTM1/p62 (#5114, Cell Signaling, Leiden, Netherlands), LC3 (#L7543; Sigma Aldrich, Darmstadt, Germany), GAPDH (#2118S, Cell Signaling, Leiden, Netherlands), and β-actin (#4970, Cell Signaling, Leiden, Netherlands). GAPDH or ß-actin were used as a loading control. After incubation with secondary horseradish peroxidase-conjugated antibodies (R&D Systems, Minneapolis, MN, USA), the blots were developed using an enhanced chemiluminescence reagent (GE Healthcare, Düsseldorf, Germany). When no signal for SIRT1 was detected in Western blot, the patient was analyzed as SIRT1-negative, while SIRT1 expression was analyzed as SIRT1-positive.
2.4. Cytokine Analysis
Cytokine release of IL4 and IL10 in plasma was measured using Flow-Cytomix™, eBioscience, Waltham, MA, USA, by flowcytometry.
2.5. Statistical Analysis
Statistical analysis was performed with GraphPad Prism, Version 18 and IBM Statistics SPSS, Version 24.
The univariate analysis was performed using Fisher’s exact test (two-sided) or the Mann–Whitney U-Test (Table 1) and the bivariate analysis was performed using a point-biserial Pearson correlation model in the case of normal distribution (Table 2). Spearman’s correlation model was applied in the context of non-normal distribution or in the case of dichotomy variables, Fisher’s exact test. The multivariate analysis was performed using a binary logistic regression with the enter method (Table 3).
All data are represented as mean ± SEM as indicated. For all tests, p values < 0.05 were considered statistically significant (* p < 0.05; ** p < 0.01; *** p < 0.001). All results were rounded to one decimal place, the r and p value were rounded to three decimal places.
3. Results
3.1. Demographic and Clinical Characteristics
During the 13-month study period, a total of 100 patients were enrolled in the study. Two patients were excluded due to missing clinical data. Of the 98 study subjects, 36 study participants were diabetic patients (36.7%) and 62 were non-diabetic controls (63.3%) (Figure 1). Within the diabetic group, patients were already diagnosed with T2DM and received antidiabetic therapy. Amon them, seven patients were diagnosed with T2DM 6 months prior to study inclusion. The group of diabetic patients (n = 36) showed an equally balanced sex ratio of female (n = 17) and male (n = 19) patients, while the group of non-diabetic controls (n = 62) had significantly more females (n = 43) than males (n = 19) (Table 1). Age ranges of diabetic patients (26–85) and non-diabetic controls (18–78) were comparable. However, the age mean of the diabetic patients was 58.8 years while the age mean for the non-diabetic controls was 41.3 years (p < 0.0001). The analysis of the body mass index (BMI) revealed elevated values for the diabetic study participants (35.15) as well as for the non-diabetic controls (36.15). The group of diabetic patients had elevated glucose levels with a mean of 140.74 mg/dL and increased HbA1c levels of 7.21%, while the mean of the glucose level for the non-diabetic control was in a normal range at 88.62 mg/dl and the HbA1c at 5.46%. The diabetic patients showed more underlying diseases and consequently a higher percentage of them were on medications to treat those diseases (Table 1).
3.2. Reduced SIRT1 in PBMCs of Diabetic Patients Is Associated with Aging
T2DM has been associated with low SIRT1 protein levels in PBMCs [24]. By contrast, SIRT1 has also been shown to be increased in PBMCs from diabetic patients with complications such as retinopathy [25]. To investigate SIRT1 expression in PBMCs in our cohort, we analyzed SIRT1 expression by Western blotting. Strikingly, the number of patients who were SIRT1-positive was significantly decreased in PBMCs of diabetic patients compared to non-diabetic controls (Figure 2, Table 1).
Next, we correlated SIRT1 expression with clinical parameters to analyze which factors are associated with loss of SIRT1 in diabetic patients. Using bivariate analysis, we found that loss of SIRT1 was associated with increased age (p < 0.0001) (Table 2). Moreover, study patients with T2DM and fat metabolism disorders showed significantly reduced levels of SIRT1 (p < 0.001) (Table 2). Furthermore, we detected a significant inverse correlation of SIRT1 expression and blood sugar levels in our study cohort (p < 0.001) (Table 2). Finally, we further performed a multivariate analysis, which confirmed that loss of SIRT1 expression significantly correlated with age (p < 0.04) (Table 3). Taken together, our results reveal that T2DM is associated with age-dependent, reduced SIRT1 expression.
3.3. Decreased SIRT1 Expression Is Associated with Decreased LC3 II/I Levels and p62 Levels
Having found that SIRT1 expression decreased with age in our cohort, we next sought to identify the impact of reduced SIRT1 levels on major signaling pathways. Since we previously showed that SIRT1 is degraded during bacterial infection, which in turn prevents autophagy [17], we investigated if reduced SIRT1 could be associated with autophagy in diabetic patients. We therefore investigated the expression of the autophagy marker proteins LC3 and p62 in PBMCs from eight SIRT1-positive study participants and seven SIRT1-negative study participants. Western blot analysis showed reduced LC3II/-I conversion in PBMCs from SIRT1-negative study participants, indicating inhibited autophagy (Figure 3A,B). Further analysis of p62 revealed elevated p62 levels in SIRT1-positive study participants while the SIRT1-negative study participants showed reduced p62 levels (Figure 3A,C). Finally, plasma anti-inflammatory cytokines such as IL4 (Figure 3D) and IL10 (Figure 3E) were significantly reduced in PBMC SIRT1-negative patients compared to SIRT1-positive patients, suggesting reduced anti-inflammatory responses in SIRT-1-negative patients. In summary, our results suggest that age-dependent reduction in SIRT1 in diabetic patients is associated with reduced conversion of LC3 I to II, represented as a ratio of LC3II/I, which is accompanied by reduced p62 levels indicative of reduced autophagy.
4. Discussion
SIRT1 has been identified as an important regulator of metabolic diseases, including T2DM, in recent years. Moreover, we and others have reported the role of SIRT1 in regulating innate immune defense mechanisms, such as autophagy, towards bacterial infections [17,22]. Diabetic patients often suffer from inflammation-mediated complications and are at a higher risk of common infections [5]. However, it is not known whether loss of SIRT1 in diabetic patients explains the predisposition towards infection by inhibiting autophagy.
Here, we report that SIRT1 was reduced in PBMCs from diabetic patients in an age-dependent manner in a cohort of 98 patients. Interestingly, reduced SIRT1 levels in PBMCs correlated with reduced LC3II/I ratio and p62 expression, suggesting an important role for SIRT1 and autophagy in regulating anti-inflammatory immune responses in these patients.
In recent years, the role of SIRT1 in the context of diabetes has been investigated in many different aspects. For example, genetic polymorphisms within SIRT1 have been associated with the development of diabetes [26,27]. Additionally, SIRT1 was shown to regulate glucose-dependent insulin secretion [28]. Also, T2DM has been associated with reduced SIRT1 expression in PBMCs [24]. In line with these results, our present findings confirmed that T2DM is associated with reduced SIRT1 expression in PBMCs, which contain a broad range of immune cells.
Moreover, SIRT1 has been linked to extended life span in animal models, indicating an age-dependent decline [29]. However, little is known about the correlation between age and SIRT1 expression in human PBMCs. One study has found decreased SIRT1 mRNA expression in PBMCs from elderly study participants compared to younger subjects [30]. Consistently, we observed an age-dependent reduction in SIRT1 protein levels in the PBMCs of our cohort.
Autophagy is an evolutionary conserved mechanism of “self-eating”, by which cells degrade damaged proteins or cell organelles in response to stress. Here, we report that loss of SIRT1 is associated with reduced LC3II/I ratios, representing reduced autophagy in T2DM patients and older people. Intriguingly, reduced SIRT1 levels also correlate with a decline in p62. This could imply enhanced autophagic turnover, as p62 is an adaptor protein that targets cargo into autophagosomes for degradation, and p62 itself is degraded in the process. However, recent studies have also shown that p62 serves as a platform for autophagosome formation [31]. Therefore, SIRT1-dependent loss of p62 could contribute to reduced autophagosome formation. Whether reduced SIRT1 leads to increased autophagic flux-dependent degradation of p62 or if SIRT1 regulates the expression of the p62 and p62 platform for autophagosome formation is an interesting research avenue for future investigation.
Our study has several limitations with regard to the patient selection. First of all, the clinical and laboratory value data were incomplete. Furthermore, the patients selected for the control group included patient with dyslipidemia. Moreover, due to the retrospective design, the groups were not matched for age. Thus, prospective studies are needed to further investigate the role of SIRT1 in aging.
Taken together, our findings show that SIRT1 is highly reduced in the PBMCs of the elderly population studied and in diabetic patients. Furthermore, a decline in SIRT1 is associated with reduced autophagy in T2DM patients. Thus, SIRT1 could possibly serve as a marker for autophagy associated with T2DM and aging. Our studies have previously shown that loss of SIRT1 exacerbates inflammation upon infection [17]. Therefore, we predict that reduced SIRT1 could be associated with inflammaging and increased inflammation in diabetes patients, which needs further investigation.
Author Contributions
Conceptualization, J.F., P.H. and N.R.; methodology, J.F., R.G., P.H., N.R.; software, S.T., J.F.; validation, J.F., P.S., N.R.; formal analysis, J.F., S.T., N.R.; investigation, N.J.H., S.T., H.B., A.N., S.W.; resources, J.S.-P., R.H., K.R., N.Q., I.S., C.L., G.P., M.F.; data curation, J.F., N.R.; writing—original draft preparation, J.F., N.J.H., C.C. and N.R.; writing—J.F., N.J., N.R.; visualization, J.F., S.T. and N.R.; supervision, J.F., P.H. and N.R.; project administration, J.F. and N.R.; funding acquisition, J.F., P.H. and N.R. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by funding from the German Center for Infectious Research (DZIF, CL-02-2011, 80185MLJFI), the Gusyk supporting position by the medical faculty of the University of Cologne and the medical faculty of Münster (No. 2024_002). The authors declare no competing financial interests.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the University Hospital of Cologne (File No.: 12-164; approval date 16 August 2012) and the Ärztekammer Nordrhein (File No.: 2012421 approval date 5 February 2013).
Informed Consent Statement
Written informed consent has been obtained from the patient(s) to conduct the study.
Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.
Acknowledgments
We would like to thank the Robinson’s lab members for the helpful discussion and Jennifer Klimek for technical support.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1.
Flowchart of patient enrolment into the Sirtuin1 diabetic study.
Figure 2.
Reduced Sirtuin1 positivity in PBMCs from diabetic patients in Western blot analysis correlates to increased age. (A) Example: Western blot analyzing SIRT1 expression in PBMCs of four non-diabetic controls and five diabetic patients showing reduced SIRT1 expression in diabetic patients. (B) Analysis of SIRT1 expression of all study subjects to age using Mann–Whitney U test (p = 0.005 = ***) showing increased age among PBMC SIRT1-negative patients. (C) Densitometric analysis of Western blot expression of PBMC SIRT1-positive patients in relation to age.
Figure 2.
Reduced Sirtuin1 positivity in PBMCs from diabetic patients in Western blot analysis correlates to increased age. (A) Example: Western blot analyzing SIRT1 expression in PBMCs of four non-diabetic controls and five diabetic patients showing reduced SIRT1 expression in diabetic patients. (B) Analysis of SIRT1 expression of all study subjects to age using Mann–Whitney U test (p = 0.005 = ***) showing increased age among PBMC SIRT1-negative patients. (C) Densitometric analysis of Western blot expression of PBMC SIRT1-positive patients in relation to age.
Figure 3.
Decreased Sirtuin1 protein levels in PBMCs from diabetic patients correlates with reduced p62 and decreased LC3 II/I ratio. p values < 0.05 were considered statistically significant (* p < 0.05; ** p < 0.01) (A) Western blot analyzing p62, LC3, and Gapdh expression in PBMCs of four SIRT1-positive and three SIRT1-negative patients. (B) Bar graph of the LC3II/I ratio from eight SIRT1-positive and seven SIRT1-negative patients. (C) Bar graph of the p62 to Gapdh ratio from eight SIRT1-positive and seven SIRT1-negative patients. (D) Cytokine analysis in the plasma of SIRT-1-positive and SIRT1-negative showing IL4 and (E) IL10.
Figure 3.
Decreased Sirtuin1 protein levels in PBMCs from diabetic patients correlates with reduced p62 and decreased LC3 II/I ratio. p values < 0.05 were considered statistically significant (* p < 0.05; ** p < 0.01) (A) Western blot analyzing p62, LC3, and Gapdh expression in PBMCs of four SIRT1-positive and three SIRT1-negative patients. (B) Bar graph of the LC3II/I ratio from eight SIRT1-positive and seven SIRT1-negative patients. (C) Bar graph of the p62 to Gapdh ratio from eight SIRT1-positive and seven SIRT1-negative patients. (D) Cytokine analysis in the plasma of SIRT-1-positive and SIRT1-negative showing IL4 and (E) IL10.
Table 1.
Clinical characteristics of included study patients comparing DMT2 and non-diabetic controls analyzed by Fisher’s exact test or Mann–Whitney U-Test. p values < 0.05 were considered statistically significant (** p < 0.01; *** p < 0.001).
Table 1.
Clinical characteristics of included study patients comparing DMT2 and non-diabetic controls analyzed by Fisher’s exact test or Mann–Whitney U-Test. p values < 0.05 were considered statistically significant (** p < 0.01; *** p < 0.001).
| Characteristics n = 98 (%) | T2DM n = 36 (36.7) | Non-Diabetic Controls n = 62 (63.3) | p |
|---|---|---|---|
| Sex | |||
| Male | 19 (52.8) | 19 (30.6) | |
| Female | 17 (47.2) | 43 (69.4) | |
| Age in years | 0.000 *** | ||
| Range | 26—85 | 18—78 | |
| Mean | 58.84 | 41.31 | |
| Std. Deviation | 15.54 | 13.08 | |
| Body Mass Index in kg/m2 | 1.000 | ||
| Missing n = 28/98 | 1 (2.8) | 27 (43.5) | |
| Range | 21.31—69.14 | 20.54—68.51 | |
| Mean | 35.15 | 36.15 | |
| Std. Deviation | 10.44 | 12.24 | |
| Blood sugar in g/dL | 0.000 *** | ||
| (norm < 100 mg/dL) | |||
| Missing n = 35/98 | 2 (5.6) | 33 (53.2) | |
| Range | 69—383 | 67—126 | |
| Mean | 140.74 | 88.62 | |
| Std. Deviation | 66.84 | 12.16 | |
| Follow up blood sugar (n = 5) | |||
| Range | 89-98 | ||
| Mean | 94.8 | ||
| Std. Deviation | 3.96 | ||
| HBa1c in % | 0.000 *** | ||
| (norm. 4-6%) | |||
| Missing n = 47/98 | 2 (5.6) | 45 (72.6) | |
| Range | 4.70—13.80 | 4.90—6.10 | |
| Mean | 7.21 | 5.46 | |
| Std. Deviation | 1.64 | 0.39 | |
| Total Cholesterol in mg/dL | 0.726 | ||
| Missing n = 45/98 | 13 (36.1) | 32 (51.6) | |
| Range | 141—262 | 135—270 | |
| Mean | 203.7 | 200.5 | |
| Std. Deviation | 32.19 | 37.11 | |
| HDL in mg/dL | 0.093 | ||
| Missing n = 43/98 | 13 (36.1) | 40 (64.5) | |
| Range | 18—69 | 25—75 | |
| Mean | 43.83 | 50.95 | |
| Std. Deviation | 12.423 | 15.299 | |
| LDL in mg/dL | 0.438 | ||
| Missing n = 54/98 | 14 (38.9) | 40 (64.5) | |
| Range | 64—199 | 83—184 | |
| Mean | 133.23 | 130.82 | |
| Std. Deviation | 28.350 | 33.516 | |
| Triglyceride in mg/dL | 0.099 | ||
| Missing n = 40/98 | 8 (22.2) | 32 (51.6) | |
| Range | 60—627 | 43—444 | |
| Mean | 202.71 | 154.10 | |
| Std. Deviation | 130.187 | 87.738 | |
| Underlying conditions | |||
| Cardiovascular n = 48/98 | 26 (72.7) | 22 (35.5) | |
| Fat metabolism n = 24/98 | 16 (44.4) | 8 (12.9) | |
| Psychiatric n = 22/98 | 12 (33.3) | 10 (16.1) | |
| Gastrointestinal n = 17/98 | 12 (33.3) | 5 (8.1) | |
| Sirt1 expression PBMC | 0.004 ** | ||
| Positive n = 31 (31.6) | 5 (13.9) | 26 (41.9) | |
| Negative n = 67 (68.4) | 31(86.1) | 36 (58.1) |
Table 2.
Bivariate analysis using point-biserial Pearson correlation model of SIRT1 positive and negative PBMCs comparing clinical characteristics. p values < 0.05 were considered statistically significant (** p < 0.01).
Table 2.
Bivariate analysis using point-biserial Pearson correlation model of SIRT1 positive and negative PBMCs comparing clinical characteristics. p values < 0.05 were considered statistically significant (** p < 0.01).
| (%) | PBMCs SIRT1 Positive | PBMCs SIRT1 Negative | R | p |
|---|---|---|---|---|
| Sex | 0.504 | |||
| Male n = 38 | 10 (32.3) | 28 (41.8) | ||
| Female n = 60 | 21 (67.7) | 39 (58.2) | ||
| Age (y) | 39.26 ± 12.57 | 51.73 ± 16.49 | −0.346 | 0.000 ** |
| BMI (kg/m2) | 37.26 ± 12.41 | 35.05 ± 10.93 | 0.063 | 0.605 |
| Past medical history | ||||
| Cardiovascular disease n = 48 | 12 (38.7) | 36 (53.7) | 0.196 | |
| Diabetes Type II n = 36 | 5 (16.1) | 31 (46.3) | 0.006 ** | |
| Fat metabolism disorder n = 24 | 1 (3.2) | 23 (34.3) | 0.001 ** | |
| Gastro-intestinal disease n = 17 | 3 (9.7) | 14 (20.9) | 0.253 | |
| Mental illness n = 22 | 5 (16.1) | 17 (25.4) | 0.436 | |
| Metabolic Variables | ||||
| Fasting blood sugar (mg/dL) | 94.53 ± 26.64 | 124,96 ± 61.69 | −0.340 | 0.006 ** |
| HbA1c (%) | 6.06 ± 1.11 | 6.83 ± 1.68 | −0.252 | 0.074 |
| Total cholesterol (mg/dL) | 213.19 ± 34.70 | 195.37 ± 44.5 | 0.165 | 0.232 |
| HDL (mg/dL) | 50.5 ± 14.91 | 46.4 ± 14.1 | 0.101 | 0.510 |
| LDL (mg/dL) | 140.00 ± 41.35 | 129.68 ± 27.15 | 0.038 | 0.804 |
| Triglyceride (mg/dL) | 169.94 ± 97.39 | 180.48 ± 118.07 | −0.30 | 0.823 |
Table 3.
Multivariate analysis of SIRT1 expression versus clinical characteristics using logistic regression. p values < 0.05 were considered statistically significant (* p < 0.05).
Table 3.
Multivariate analysis of SIRT1 expression versus clinical characteristics using logistic regression. p values < 0.05 were considered statistically significant (* p < 0.05).
| Independent Variables | B (SE) | Odds Ratio | 95 % C.I. for Odds Ratio Lower Upper | p | |
|---|---|---|---|---|---|
| Age | 0.059 (0.029) | 0.943 | 0.891 | 0.997 | 0.040 * |
| Sex | 0.108 (0.682) | 1.114 | 0.292 | 4.240 | 0.875 |
| Cardiovascular disease | 1.130 (0.772) | 3.096 | 0.682 | 14.062 | 0.143 |
| Diabetes Type II | 1.262 (0.879) | 3.533 | 0.631 | 19.792 | 0.151 |
| Fat metabolism disorder | −4.476 (2.646) | 0.011 | 0.000 | 2.034 | 0.091 |
| Gastrointestinal disease | 0.405 (1.165) | 1.5 | 0.153 | 14.715 | 0.728 |
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Fischer, J.; Hos, N.J.; Tritschler, S.; Schmitz-Peters, J.; Ganesan, R.; Calabrese, C.; Schiller, P.; Brunnert, H.; Nowag, A.; Winter, S.; et al. Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM). Diabetology 2025, 6, 45. https://doi.org/10.3390/diabetology6060045
AMA Style
Fischer J, Hos NJ, Tritschler S, Schmitz-Peters J, Ganesan R, Calabrese C, Schiller P, Brunnert H, Nowag A, Winter S, et al. Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM). Diabetology. 2025; 6(6):45. https://doi.org/10.3390/diabetology6060045
Chicago/Turabian StyleFischer, Julia, Nina Judith Hos, Sophie Tritschler, Joel Schmitz-Peters, Raja Ganesan, Chiara Calabrese, Petra Schiller, Hannah Brunnert, Angela Nowag, Sandra Winter, and et al. 2025. "Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)" Diabetology 6, no. 6: 45. https://doi.org/10.3390/diabetology6060045
APA StyleFischer, J., Hos, N. J., Tritschler, S., Schmitz-Peters, J., Ganesan, R., Calabrese, C., Schiller, P., Brunnert, H., Nowag, A., Winter, S., Hanßen, R., Römer, K., Qurishi, N., Suarèz, I., Jung, N., Lehmann, C., Plum, G., Faust, M., Hartmann, P., & Robinson, N. (2025). Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM). Diabetology, 6(6), 45. https://doi.org/10.3390/diabetology6060045
