A plasma proteomic signature of mitochondrial dysfunction and its diagnostic potential for Type 2 Diabetes Mellitus

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Hypomagnesaemia has been reported in type 2 diabetes mellitus (T2DM) and an association of low serum magnesium (Mg) with insulin resistance has been observed. In this cross-sectional study, 65 new T2DM patients and 65 healthy controls were investigated to assess the Mg status and see the association between Mg level and insulin resistance. Oral glucose tolerance test, HbA1c, serum Mg, and fasting insulin were measured and the level of insulin resistance was calculated by using the homeostasis model assessment for insulin resistance (HOMA-IR). Serum Mg level was similar in T2DM and control groups; a higher frequency of hypomagnesemia was observed in the T2DM than control group (26.2% vs. 12.3%) though it was not statistically significant (p= 0.074). Level of insulin resistance (HOMA-IR) was higher in the T2DM group and a higher frequency of subjects had insulin resistance in this group compared to controls. No significant differences in age, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, fasting insulin level and HOMA-IR were observed between normomagnesaemic and hypomagnesaemic T2DM subjects. In the T2DM group, age, BMI, WC, WHR, FPG, fasting insulin and HOMA-IR correlated with serum Mg level though in the control group Mg had significant inverse correlations with BMI and fasting insulin. New T2DM subjects and healthy controls had similar Mg status although the frequency of hypomagnesemia was higher (not significant) in the T2DM group and serum Mg level had no correlation with glycemic status, fasting insulin and HOMA-IR in T2DM patients.

Objective To evaluate positive rate of serum tissue transglutaminase antibody (tTGA), which is a specific antibody of celiac disease (CD), and clinical symptoms of CD in patients with type 1 diabetes mellitus (T1DM). Methods T1DM (n=130) and type 2 diabetes mellitus (T2DM) (n=178) patients with disease course less than 12 months were recruited. 109 healthy volunteers were recruited as control group. The general data of all subjects were recorded and clinical symptoms of CD collected through screening tables. Fasting plasma glucose (FPG) and HbA1c were measured. The levels of tTGA were detected by radioligand assay. T1DM patients were divided into juvenile T1DM group (age ≤18 years) and adult T1DM group (age> 18 years), and the positive rate of tTGA was analyzed in T1DM patients with different ages. In addition, T1DM patients were classified to tTGA-positive group and tTGA-negative group, and the correlation between clinical symptoms and tTGA levels were evaluated. Quantitative data were analyzed by t-test or one-way ANOVA and enumeration data were accessed by Chi-square test. Results The positive rate of tTGA in patients with T1DM was significantly higher than that in patients with T2DM and in control subjects (19.2% vs 2.2%, 19.2% vs 0.9%, respectively, χ2=13.466-33.879, both P<0.05). The positive rate of tTGA in juvenile T1DM group was higher than that in adult T1DM group (26.7% vs 12.9%, χ2=3.967, P=0.046). The incidence of CD-related clinical symptoms (≥ 1 CD symptoms and ≥ 3 CD symptoms) in tTGA-positive patients was significantly higher than those in tTGA-negative patients (64.0% vs 19.0%, 24.0% vs 5.7%, respectively, χ2=20.377-8.058, both P<0.05). The top three highest incidence of CD-related clinical symptoms were: (1) chronic abdominal pain, diarrhea, abdominal distension (9/25, 36.0%);(2) weight loss, fatigue (8/25, 32.0%); (3) nausea, vomiting (6/25, 24.0%). Conclusion TTGA should be routinely screened in T1DM patients and this would contribute to early prevention and diagnosis of CD. TTGA-positive patients with typical clinical symptoms of CD should be further confirmed by small intestinal mucosal biopsy and administrated treatment when necessary. Key words: Diabetes mellitus, type 1; Celiac disease; Tissue transglutaminase antibody

Objective: To explore the correlation between diabetic cognitive impairment (DCI) and diabetic retinopathy (DR) through examining the cognitive function and the metabolism of the cerebrum in Type 2 diabetes mellitus (T2DM) by 1H-MRS.Methods: Fifty-three patients with T2DM were enrolled for this study. According to the fundus examination, the patients were divided into the DR group (n = 26) and the T2DM without DR group (T2DM group, n = 27). Thirty healthy adults were selected as a control group (HC group, n = 30). Cognitive function was measured by Montreal Cognitive Assessment (MoCA). The peak areas of N-acetylaspartate (NAA), Cho-line (Cho), Creatine (Cr), and Myo-inositol (mI) as well as their ratios were detected by proton magnetic resonance spectroscopy (1H-MRS). The difference analysis between the three groups was performed by one-way ANOVA. When p < 0.05, LSD-t was applied. A partial correlation analysis (with age as a covariate) was used to analyze the correlation between metabolites in the DR group and MoCA scores. Among all T2DM patients, Chi-square test age, gender, education level, BMI, SBP, DBP, FPG, HbA1c, TC, TG, HDL-C, LDL-C, DR, and DCI correlation were measured. Differences were statistically significant while P < 0.05.Results: 1. The scores of MoCA in the DR group or in the T2DM group were significantly less than those in the HC group (F = 3.54, P < 0.05), and the scores of MoCA in the DR group were significantly less than those in the other groups (F = 3.61, P < 0.05). 2. There were significant differences for NAA in the bilateral hippocampus in DR patients, T2DM patients, and healthy controls (P < 0.05). 3. The NAA/Cr was significantly positively correlated with the score of MoCA in DR patients' left hippocampus (r = 0.781, P < 0.01). 4. Chi-square analysis found that there was a correlation between DR and DCI (x2 = 4.6, df = 1, p = 0.032, plt: 0.05). There was no correlation between other influencing factors and DCI (P > 0.05).Conclusion: DCI is closely correlated with the DR in patients with T2DM. Hippocampal brain metabolism may have some changes in two sides of NAA in patients with DR, 1H-MRS may provide effective imaging strategies and methods for the early diagnosis of brain damage and quantitative assessment cognitive function in T2DM.

To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously decreased (all P<0.05); lowest saturation oxygen (LSpO₂) was significantly increased [(92.3 ± 3.7)% vs (81.5 ± 20.2)%, P<0.001]; the alarming times and HOMA-IR were obviously decreased (P=0.019, 0.043). According to multiple linear regression analysis, the AHI (β=0.736, P<0.001) in OSAHS with T2DM group was positively related to the average dynamic glucose level during sleep time, but the LSpO₂(β=-0.889, P<0.001) was negatively correlated. OSAHS patients with newly diagnosed T2DM have higher glucose level than that in simple T2DM patients, and CPAP therapy can obviously decrease the glucose level in newly diagnosed T2DM patients with OSAHS. AHI and LSpO₂may influence the average dynamic glucose level during sleep time.

This study aimed to explore the risk factors attributed to osteoporosis in newly type 2 diabetes mellitus (T2DM) patients. This study aimed to recruit 244 T2DM patients and 218 non-diabetic controls. We collected demographic characteristics, medical history, bone mineral density and biomarkers including bone specific alkaline phosphatase (BALP), osteocalcin, N-terminal peptide of type I procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRCAP-5b), β-Cross Laps of type I collagen-containing cross-linked C-telopeptide (β-CTX), 25-hydroxyvitamin D, parathyroid hormone were recorded or detected. Bone mineral density (BMD) was our primary outcome. Based on the result of BMD, we divided both the control group and T2DM group into three subgroups: normal bone mass, osteopenia and osteoporosis. In control group, we found age, sex, menopausal status, BMI, P1NP, BALP, TRACP-5b, osteocalcin, and corrected serum calcium are differential among three subgroups. In T2DM group, we found age, sex, menopausal status, drinking status, BMI, HbA1c, TRACP-5b and OC were differential among three subgroups. In T2DM and control groups, age, female, postmenopausal status, BALP, TRACP-5b and osteocalcin were positively correlated while BMI was negatively correlated with osteoporosis. In control group, β-CTX was positively correlated with osteoporosis. In T2DM group, HbA1c and corrected serum calcium concentration were positively correlated with osteoporosis. After further adjustment of age, BMI in male, TRACP-5b was positively correlated with the risk of osteoporosis in newly diagnosed T2DM. After adjusted of age, BMI and menopausal status in female, OC was positively correlated with the risk of osteoporosis in newly diagnosed T2DM and controls. In female T2DM, BALP and P1NP were positively correlated with the risk of osteoporosis. In conclusion, age, BMI and menopausal status are common risk factors for osteoporosis in diabetic and non-diabetic patients, however TRACP-5b, BALP and osteocalcin are special risk factors for osteoporosis in newly diagnosed T2DM patients but not non-diabetic patients, which may be applied to identify osteoporosis risk in T2DM patients, but this result needs to be proven with fracture data.

This doctoral thesis is based on the publication of 2 studies that aim to determine if the variability of glycemia, evaluated with continuous glucose monitoring (CGM), presents a circadian rhythm in patients with diabetes mellitus (DM) type I and II. Study I. Daily glucose variability is higher in diabetic mellitus (DM) patients which has been related to the severity of the disease. However, it is unclear whether glycemic variability displays a specific pattem oscilation or if it is completeiy random. Thus, to determine glycemic variability pattern, we measured and analyzed continuous glucose monitoring (CGM) data, in control subjects and patients with DM type-1 (T1D). CGM data was assessed for 6 days (day: 08:00-20:00-h; and night: 20:00- 08:00-h). Participants (n=172; age= 18-80 years) were assigned to T1D (n= 144, females=65) and control (i.e., healthy; n=28, females=22) groups. Anthropometry, pharmacologic treatments, glycosylated hemoglobin (HbAlc) and years of evolution were determined. T1D females displayed a higher glycemia at 10:00-14:00-h vs. T1D males and control females. DM patients displays mainly stationary oscillations (deterministic), with circadian rhythm characteristics. The glycemia oscillated between 2 and 6 days. The predictive model of glycemia showed that it is possible to predict hyper and hypoglycemia (R2=0.94 and 0.98, respectively) in DM patients independent of their etiology. Our data showed that glycemic variability had a specific oscillation pattern with circadian characteristics, with episodes of hypoglycemia and hyperglycemia at day phases, which could help therapeutic action for this population. Study II. The objective of study 2 was to determine the characteristics of glycemic oscillations in T2D and to verify if they can be predicted over time in patients. Daily glucose variability is reported to be higher in patients with diabetes mellitus (DM) than in the general population. Specific oscillatory patterns of glycemic control are knovn to exist on patients with type 1 DM (T1D), but it is unclear whether the same is true for patients with type 2 DM (T2D). Here, we seek to determine patterns of glycemic variability in T2D patients using continuous glucose monitoring. Data were evaluated for 6 continuous days (day: 08:00-20:00; and night: 20:00---08:00). Participants were assigned to T2D (n=24, women= 10) and control (ie, healthy; n=28, women=22) groups. The results showed that glycosylated hemoglobin, blood glucose and body mass index were higher in T2D patients than in controls (all p&lt;0.05). Furthermore, the time in hyperglycemia and euglycemia was markedly longer and shorter, respectively, in the T2D group (p&lt;0.05) with no significant difference for time in hypoglycemia. The data on glycemic variability revealed that the values of the standard deviation, the coefficient of variation and the total power of glycemic variability were significantly higher in the T2D group than in the control group (p&lt;0.05). In addition, oscillatory pattens were significantly different between groups (p=0.032): the control group was mainly distributed at 2-3 and &gt;6 days, while the T2D group showed a more homogeneous distribution at 2-3 days. &gt;6 days. The glycemia predictive model, previously used in DM1, demonstrated that it is possible to accurately predict hyperglycemic and hypoglycemie events (R2=0.97 and 0.98, respectively). Therefore, like what is observed in T1D, patients with T2D exhibit specific oscillatory pattens of glycemíc control, which are possible to predict. These findings may help improve the treatment of DM by considering the individual oscillatory patterns of patients.

BackgroundThere existed evidence that type 2 diabetes mellitus (T2DM) prevalence and control rate have seasonal variation. Our study aimed to examine the ambient temperature and fasting plasma glucose (FPG) association and estimate temperature-adjusted T2DM prevalence and control rate.MethodsFour cross-sectional health surveys with 26,350 respondents were conducted in Guangdong Province from 2007 to 2015. Multistage cluster sampling was used to recruit study participants. The data of demographic characteristics, lifestyle factors, diet and use of hypoglycemic medicine, height, weight, FPG and meteorological information were collected. And an inverse distance-weighted method was employed to estimate daily temperature exposures at the individual’ s residential district/county. Base on World Health Organization 2006 criteria, participants were divided into normal fasting glucose (NFG) participants (n = 23,877), known T2DM patients (n = 916) and newly detected T2DM patients (n = 1557). Generalized additive mixed model was employed to evaluate the nonlinear associations between temperature and FPG among different T2DM subgroups. The T2DM prevalence and control rate were estimated based on temperature-FPG association.ResultsThe curves of temperature and FPG were downward parabola for total, NFG and known T2DM groups, while it was “U”-shaped for newly detected T2DM patients. When temperature decreased from 30 °C to 4 °C, the FPG significantly increased 0.24 (95%CI: 0.15, 0.33) mmol/L, 0.10 (95%CI: 0.06, 0.14) mmol/L and 1.34 (95%CI: 0.56, 2.12) mmol/L in total, NFG and known T2DM groups, respectively. Compared to 19 °C, newly detected T2DM patients’ FPGs were increased 0.73 (95%CI: 0.13, 1.30) mmol/L at 4 °C and 0.53 (0.00, 1.07) mmol/L at 30 °C. The model-estimated temperature-adjusted T2DM prevalence had a down and up trend, with 9.7% at 5 °C, 8.9% at 20 °C and 9.4% at 30 °C, respectively. At 5, 10, 15, 20, 25 and 30 °C, the model-estimated temperature-adjusted T2DM control rates were 33.2, 35.4, 38.2, 43.6, 49.1 and 55.2%.ConclusionTemperature was negatively associated with FPG for NFG and known T2DM subgroups, while their association was U-shape for newly detected T2DM patients. Hence, the temperature-adjusted T2DM prevalence show a dip/peak pattern and T2DM control rate display a rising trend when temperature increase. Our findings suggest temperature should be considered in T2DM clinic management and epidemiological survey.

Objective To investigate the effects of short term insulin pump intensive therapy on flow-mediated dilation (FMD) in type 2 diabetes mellitus (T2DM) patients with and without vascular complications. Methods Seventy-six patients with T2DM (T2DM group) were divided into 2 subgroups: T2DM1 subgroup (28 patients with vascular complications) and T2DM2 subgroup (48 patients without vascular complications). Meanwhile, 30 healthy cases were selected as NC group. All research subjects accepted high-frequency ultrasound detection on brachial artery for FMD. After insulin pump intensive therapy,FMD in T2DM group was reexamined, fasting insulin was detected and HOMA-IR was calculated. Results Compared with that in NC group, FMD in T2DM group was significantly lower(P＜ 0.01). However, glycosylated hemoglobin (HbA1c ), fasting plasma glucose (FPG ),H0MA-IR and blood fat were significantly higher (P＜0.01 or ＜0.05). Correlation analysis showed that FMD had negative correlation with HbA1c, FPG, HOMA-IR, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C)(P＜0.01),and had positive correlation with high-density lipoprotein cholesterol (HDL-C). After 2 weeks of insulin pump therapy, the improvement of FMD between the two groups was different. FMD in T2DM1 subgroup increased from (4.25 ± 1.96)% to (4.96 ± 1.36)%(P＞0.05), and FMD in T2DM2 subgroup increased from (4.02 ± 2.35)% to (7.56 ± 2.34)%(P＜ 0.01). Conclusion Insulin pump intensive therapy can evidently improve FMD in T2DM patients without vascular complications. Key words: Insulin infusion systems; Diabetes mellitus, type 2; Vasodilation

According to the 'Th(1)/Th(2) paradigm', children with type 1 diabetes mellitus (T1DM) should have a lower risk of developing allergic sensitization and, because of the involvement of insulin in modulating airway inflammation, different frequency or severity in allergy-related respiratory manifestations. This article aims at evaluating the frequency and type of allergic sensitization and its respiratory manifestation, asthma and/or rhinitis, in a group of pediatric patients with T1DM. Patients (112) with T1DM, 7.8-16.9 yr of age (63 males and 49 females) were evaluated. Skin prick test (SPT) reactivity to the most common classes of aeroallergens were performed and compared with data obtained in 709 school-aged children. The frequency of sensitization was not different in the T1DM and in the control subjects (43.7% and 40.8%, respectively; p = 0.55), with similar proportions of individuals sensitized to one allergen (32.7% and 38.1%, respectively; p = 0.47). In both groups, sensitization to house dust mite allergens was the most frequently detected (69.4% and 65.4%, respectively; p = 0.59), with a higher proportions of individuals sensitized to Graminae (+Cynodon dactylon; p < 0.0001) and a lower, but weakly significant, proportion sensitized to Parietaria (p = 0.03) in the T1DM group, as compared with controls. No differences were found between T1DM and control groups in the proportion of individuals reporting rhinitis (26.8% and 29.2%; p = 0.60). However, comparing separately sensitized and non-sensitized subjects, a lower proportion of rhinitis subjects was detected in the non-sensitized T1DM patients, when compared with the non-sensitized control subjects (p = 0.01). In addition, no differences were detected between T1DM and control groups in frequency of symptoms related to 'lifetime asthma', i.e., asthma episodes during life (14.3% and 16.5%, respectively: p = 0.55), also when sensitized and non-sensitized subjects were evaluated separately (p = 0.12 and p = 1.00, respectively). However, no T1DM patient had 'actual asthma', i.e., asthma episodes in the last year, vs. 5.8% of the individuals in the control group (p = 0.009), the difference being mostly ascribed to sensitized subjects (p = 0.012). Finally, out of the 16 T1DM patients with 'lifetime asthma', 15 had mild intermittent disease and only one mild persistent disease. T1DM does not seem to play a downregulating role on the development of allergic sensitization to aeroallergens, but may lower the frequency or the severity of its clinical manifestations at respiratory level.

AimsTo explore the predictive value of the IGF-1/IGFBP-3 ratio for the presence of thyroid nodules in patients with type 2 diabetes mellitus (T2DM).MethodsThis observational study prospectively enrolled patients with T2DM at the Second Hospital of Jilin University between May 2021 and January 2022. Thyroid nodule (TN) status was determined by ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of the serum IGF-1/IGFBP-3 molar ratio for TNs. Multivariable logistic regression analysis was conducted to identify risk factors for thyroid nodules in patients with T2DM.ResultsA total of 122 patients (mean age ± standard deviation: 52.57 ± 11.71 years; 74 males) were enrolled. 37.7% (n=46) of patients did not have TNs, while 62.3% (n=76) had TNs. The duration of diabetes, age, and HDL-C level were significantly higher in the T2DM group with TNs compared to the group without TNs (all P < 0.05). The area under the ROC curve (AUC) for the combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio in predicting TNs in T2DM patients was 0.619 (P < 0.001). Additionally, multivariable logistic regression analysis revealed that the duration of diabetes, age, fasting plasma glucose (FPG), fasting insulin (FINS), thyroid-stimulating hormone (TSH), IGF-1, and IGFBP-3 levels were independent risk factors for thyroid nodules, while the serum IGF-1/IGFBP-3 molar ratio level was an independent protective factor for thyroid nodules in patients with T2DM (all P < 0.05).ConclusionThe combination of IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio may have a better predictive value for TNs in T2DM patients than using any single marker alone. The duration of diabetes, age, FPG, FINS, TSH, IGF-1, IGFBP-3, and the serum IGF-1/IGFBP-3 molar ratio levels were independently associated with thyroid nodules in patients with T2DM.

Background and purposeGrowth factor receptor-bound protein 2(GRB2), a bridging protein. An animal study showed that downregulation of GRB2 inhibited the activation of PI3K/AKT/NF-kB pathway which improved lipid accumulation and inflammatory infiltration in rats with atherosclerosis (AS), resulting in an anti-AS effect. This was the first study to investigate blood GRB2 levels in type 2 diabetes mellitus(T2DM) patients with carotid atherosclerosis (CAS), exploring its relationship with various metabolic indicators, and further, examining whether GRB2 has an AS effect in patients with T2DM.MethodsA total of 203 participants were recruited in the study, including 69 T2DM patients without CAS (T2DM group), 67 T2DM patients with CAS (CAS group), and 67 in the age-sex-matched healthy subjects (Control group). Serum GRB2 levels were measured using enzyme-linked immunosorbent assay (ELISA) in 203 subjects who had received carotid ultrasonography. In addition, cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), glycosylated hemoglobin (HBA1c), fasting insulin (FINS), hypersensitive C-reactive protein (Hs-CRP), and Interleukin 6 (IL-6) were also tested. The correlation between serum GRB2 levels and other indexes was analyzed. Finally, we analyzed the risk factors affecting carotid intima-media thickness (CIMT) in T2DM patients.ResultsSerum GRB2 levels were increased in the T2DM group than in the control group, and further elevated in the CAS group (median 3.05 vs 4.40 vs 7.09 ng/ml, P<0.001). Spearman correlation analysis showed that GRB2 concentrations were negatively correlated with HDL-C, and positively associated with duration of diabetes, waist-to-hip ratio (WHR), TC, HBA1c, FPG, FINS, homeostasis model assessment-insulin resistance index (HOMA-IR), Hs-CRP, IL-6 and CIMT (P<0.01). Furthermore, serum GRB2 levels (P<0.001) remained independently related to CIMT after adjusting for the age, sex, duration of diabetes, and Body Mass Index (BMI) variables. Stepwise multiple linear regression analysis showed that IL-6, HDL-C, HBA1c, and CIMT are independent correlation factors of serum GRB2 (P<0.01). Univariate logistic regression suggested that disease duration, WHR, systolic blood pressure (SBP), TG, HDL-C, HBA1c, FPG, HOMA-IR, IL-6, Hs-CRP, and GRB2 independently associated with T2DM is combined with CAS(P<0.05). And multivariate logistic regression analysis showed that duration of diabetes, IL-6, and serum GRB2 levels were independent risk factors for T2DM combined with CAS (P<0.05), and serum GRB2 levels were a highly sensitive indicator of early AS (OR=1.405, 95% CI: 1.192-1.658 P<0.001). Moreover, the ROC curve AUC area of serum GRB2 expression levels was 0.80 (95%CI: 0.7291-0.8613, P < 0.001), with a sensitivity of 83.58% and specificity of 70.59%. The risk of CAS was substantially higher in patients with T2DM whose serum GRB2 concentration was >4.59 ng/ml.ConclusionsSerum GRB2 concentrations were significantly increased in T2DM combined with CAS, and serum GRB2 levels were linearly correlated with CIMT, suggesting that GRB2 may be involved in the occurrence and development of T2DM with CAS, which can be used as a predictor of whether T2DM is combined with CAS.

Background/Objectives: The global prevalence of obesity and type 2 diabetes mellitus (T2DM) has been steadily increasing, and these interrelated disorders share common pathophysiological mechanisms, including altered levels of adipokines secreted from adipose tissue. Among these, chemerin and visfatin have been suggested as potential biomarkers for obesity-related metabolic dysfunction. This study aimed to evaluate the relationship between serum chemerin and visfatin levels and obesity in patients with T2DM. Methods: The study included 74 obese T2DM patients, 60 non-obese T2DM patients, and 36 healthy controls. Serum chemerin and visfatin levels were measured using an enzyme-linked immunosorbent assay (ELISA). Clinical parameters including HbA1c, fasting plasma glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were assessed. Between-group comparisons were performed using appropriate parametric or non-parametric tests with Bonferroni correction for multiple comparisons. ROC curve analysis was applied to evaluate the diagnostic performance of visfatin. Results: Serum visfatin levels were significantly higher in the T2DM (33.00 ± 20.61) groups compared to controls (30.25 ± 26.40; p = 0.01), while chemerin levels showed no significant difference. HbA1c and glucose levels were elevated in both diabetic groups, whereas insulin and HOMA-IR were significantly higher only in the obese T2DM group. Receiver operating characteristic (ROC) analysis revealed limited diagnostic accuracy of visfatin (AUC < 0.70). Conclusions: Visfatin levels were modestly higher in obese T2DM patients, while chemerin did not differ significantly among groups. However, the diagnostic performance of visfatin was limited (AUC < 0.70), and these findings should be regarded as exploratory. Larger, well-controlled studies are required to clarify whether visfatin or chemerin could have any clinical utility as part of multi-marker approaches.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. Liraglutide is potentially curative for T2DM with NAFLD.