Food intake, plasma copeptin and cardiovascular risk in patients with type 2 diabetes: A cross-sectional analysis.

BACKGROUND AND AIM: Increased consumption of ultra-processed foods has been linked to both mortality and cardiovascular risk. Copeptin levels may serve as potential risk markers for cardiovascular death and events. This cross-sectional analysis seeks to assess the potential correlation between the intake of ultra-processed foods and copeptin levels in outpatients diagnosed with type 2 diabetes, based on estimates of cardiovascular risk. METHODS AND RESULTS: Outpatients underwent clinical and nutritional assessments. Dietary information was gathered using a validated quantitative food frequency questionnaire, and the consumption of all foods, beverages, and food products was assessed according to the NOVA food classification system. Fasting plasma-EDTA samples were collected and preserved at -80 °C. Plasma copeptin measurements were analyzed using an enzyme-linked immunosorbent assay based on the competition principle. Participants were categorized into two groups: high risk and very high risk, based on cardiovascular risk calculated by the HEARTS calculator. A total of 190 participants were included in the evaluation, with an average age of 60 ± 9 years, glycated hemoglobin of 8.4 ± 1.4%, and a diabetes duration of 11 (5-19) years. Patients at a very high cardiovascular risk exhibited higher plasma copeptin levels compared to those at high cardiovascular risk. Notably, 92.1% of patients reported consuming more than 10% of total energy intake from ultra-processed foods, although this proportion did not differ between the two groups. CONCLUSION: This patient sample reported elevated consumption of ultra-processed foods; nevertheless, the correlation between ultra-processed foods and plasma copeptin has not been substantiated.

Does liraglutide alleviate inflammation in brain-dead donors? A randomized clinical trial.

Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1ß, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic ( BCL2 ), endoplasmic reticulum stress markers ( DDIT3/CHOP , HSPA5/BIP ), and antioxidant ( superoxide dismutase 2 , uncoupling protein 2 ) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (-28 [-182, 135] vs. 32 [-10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (-0.01 [-2.2, 1.5] vs. 1.9 [-0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2-8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

The rs3931283/PVT1 and rs7158663/MEG3 polymorphisms are associated with diabetic kidney disease and markers of renal function in patients with type 2 diabetes mellitus.

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of gene expression. Some studies have reported the association of polymorphisms in lncRNA genes with diabetes mellitus (DM) and its chronic complications, including diabetic kidney disease (DKD); however, the results are still inconclusive. Thus, we investigated the association of the rs3200401/MALAT1, rs1894720/MIAT, rs3931283/PVT1, rs11993333/PVT1, rs5749201/TUG1, and rs7158663/MEG3 polymorphisms with DKD in patients with type 2 DM (T2DM). METHODS AND RESULTS: This study comprised 902 patients with T2DM and DKD (cases) and 394 patients with T2DM without DKD (controls). The six polymorphisms of interest were genotyped by real-time PCR using TaqMan probes. Frequency of the rs3931283/PVT1 G/G genotype was 36.2% in cases and 31.9% in controls (P = 0.331). After adjustment for gender, glycated hemoglobin, HDL cholesterol, ethnicity, hypertension, and diabetic retinopathy, the G/G genotype was associated with risk for DKD (OR = 1.625, 95% CI 1.020-2.588; P = 0.041). The rs3931283/PVT1 G/G genotype was also associated with higher urinary albumin excretion levels compared to A allele carriers (P = 0.017). No difference was found in rs7158663/MEG3 genotype frequencies between T2DM controls and DKD patients (OR = 1.087, 95% CI 0.686-1.724; P = 0.722). However, the rs7158663/MEG3 G/G genotype was associated with protection against severe DKD (OR = 0.694, 95% CI 0.488-0.989; P = 0.043, for patients with severe DKD vs. T2DM controls). The rs7158663/MEG3 G/G genotype was also associated with lower creatinine levels (P = 0.007) and higher estimated glomerular filtration rate (P = 0.010) compared to A allele carriers. No association was found between the rs11993333/PVT1, rs3200401/MALAT1, rs1894720/MIAT, and rs5749201/TUG1 polymorphisms and DKD or its laboratory markers. CONCLUSION: The rs3931283/PVT1 G/G and rs7158663/MEG3 G/G are associated with DKD and markers of renal function in T2DM patients from a Brazilian population.

The rs1800469 T/T and rs1800470 C/C genotypes of the TGFB1 gene confer protection against diabetic retinopathy in a Southern Brazilian population.

The transforming growth factor beta 1 (TGFB1) is a pro-inflammatory cytokine that plays a key role in the mechanisms of angiogenesis and breakdown of the blood-retina barrier, which are implicated in the pathogenesis of diabetic retinopathy (DR). Polymorphisms in the TGFB1 gene have been associated with DR; however, results are still contradictory. Therefore, the aim of this study was to investigate the potential association between two TGFB1 polymorphisms and DR. This study included 992 patients with diabetes mellitus (DM): 546 patients with DR (cases) and 446 patients without DR and with ≥10 years of DM (controls). The TGFB1 rs1800469 and rs1800470 polymorphisms were genotyped by real-time PCR. Frequency of rs1800469 T/T genotype was higher in controls compared to DR cases (18.3% vs. 12.7%, P= 0.022). This genotype remained associated with protection for DR, adjusting for covariables (OR= 0.604; 95% CI 0.395 - 0.923; P= 0.020, recessive model). The rs1800470 C/C genotype was observed in 25.4% of the controls and 18.0% of the cases (P= 0.015); thus, being associated with protection against DR under the recessive model (OR= 0.589; 95% CI 0.405 - 0.857; P= 0.006), adjusting for covariables. In conclusion, the TGFB1 rs1800469 and rs1800470 polymorphisms are associated with protection against DR in DM patients from Southern Brazil.

The lncRNA MALAT1 is upregulated in urine of type 1 diabetes mellitus patients with diabetic kidney disease.

Long non-coding RNAs (lncRNAs) are RNAs with >200 nucleotides that are unable to encode proteins and are involved in gene expression regulation. LncRNAs have a key role in many physiological and pathological processes and, consequently, they have been associated with several human diseases, including diabetes chronic complications, such as diabetes kidney disease (DKD). In this context, some studies have identified the dysregulation of the lncRNAs MALAT1 and TUG1 in patients with DKD; nevertheless, available data are still contradictory. Thus, the objective of this study was to compare MALAT1 and TUG1 expressions in urine of patients with type 1 diabetes mellitus (T1DM) categorized according to DKD presence. This study comprised 18 T1DM patients with DKD (cases) and 9 long-duration T1DM patients without DKD (controls). MALAT1 and TUG1 were analyzed using qPCR. Bioinformatics analyses were done to identify both lncRNA target genes and the signaling pathways under their regulation. The lncRNA MALAT1 was upregulated in urine of T1DM patients with DKD vs. T1DM controls (P = 0.007). The expression of lncRNA TUG1 did not differ between groups (P = 0.815). Bioinformatics analysis showed these two lncRNAs take part in metabolism-related pathways. The present study shows that the lncRNA MALAT1 is upregulated in T1DM patients presenting DKD.

The rs705708 A allele of the ERBB3 gene is associated with lower prevalence of diabetic retinopathy and arterial hypertension and with improved renal function in type 1 diabetic patients.

INTRODUCTION: The Erb-b2 receptor tyrosine kinase 3 (ERBB3) is involved in autoimmune processes related to type 1 diabetes mellitus (T1DM) pathogenesis. Accordingly, some studies have suggested that single nucleotide polymorphisms (SNPs) in the ERBB3 gene confer risk for T1DM. Proliferation-associated protein 2G4 (PA2G4) is another candidate gene for this disease because it regulates cell proliferation and adaptive immunity. Moreover, PA2G4 regulates ERBB3. To date, no study has evaluated the association of PA2G4 SNPs and T1DM. AIM: To evaluate the association of ERBB3 rs705708 (G/A) and PA2G4 rs773120 (C/T) SNPs with T1DM and its clinical and laboratory characteristics. METHODS: This case-control study included 976 white subjects from Southern Brazil, categorized into 501 cases with T1DM and 475 non-diabetic controls. The ERBB3 and PA2G4 SNPs were genotyped by allelic discrimination-real-time PCR. RESULTS: ERBB3 rs705708 and PA2G4 rs773120 SNPs were not associated with T1DM considering different inheritance models and also when controlling for covariables. However, T1DM patients carrying the ERBB3 rs705708 A allele developed T1DM at an earlier age vs. G/G patients. Interestingly, in the T1DM group, the rs705708 A allele was associated with lower prevalence of diabetic retinopathy and arterial hypertension as well as with improved renal function (higher estimated glomerular filtration rate and lower urinary albumin excretion levels) compared to G/G patients. CONCLUSIONS: Although no association was observed between the ERBB3 rs705708 and PA2G4 rs773120 SNPs and T1DM, the rs705708 A allele was associated, for the first time in literature, with lower prevalence of diabetic retinopathy and arterial hypertension. Additionally, this SNP was associated with improved renal function.

Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case-control study and systematic review with meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case-control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR. METHODS: The case-control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models. RESULTS: The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case-control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68-0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69-0.97), and overdominant (OR = 0.88, 95% CI: 0.79-0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR. CONCLUSION: Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation.

Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis.

Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.

-866G/A and Ins/Del polymorphisms in the UCP2 gene and diabetic kidney disease: case-control study and meta-analysis.

Uncoupling protein 2 (UCP2) decreases reactive oxygen species (ROS). ROS overproduction is a key contributor to the pathogenesis of diabetic kidney disease (DKD). Thus, UCP2 polymorphisms are candidate risk factors for DKD; however, their associations with this complication are still inconclusive. Here, we describe a case-control study and a meta-analysis conducted to investigate the association between UCP2 -866G/A and Ins/Del polymorphisms and DKD. The case-control study comprised 385 patients with type 1 diabetes mellitus (T1DM): 223 patients without DKD and 162 with DKD. UCP2 -866G/A (rs659366) and Ins/Del polymorphisms were genotyped by real-time PCR and conventional PCR, respectively. For the meta-analysis, a literature search was conducted to identify all studies that investigated associations between UCP2 polymorphisms and DKD in patients with T1DM or type 2 diabetes mellitus. Pooled odds ratios were calculated for different inheritance models. Allele and genotype frequencies of -866G/A and Ins/Del polymorphisms did not differ between T1DM case and control groups. Haplotype frequencies were also similar between groups. Four studies plus the present one were eligible for inclusion in the meta-analysis. In agreement with case-control data, the meta-analysis results showed that the -866G/A and Ins/Del polymorphisms were not associated with DKD. In conclusion, our case-control and meta-analysis studies did not indicate an association between the analyzed UCP2 polymorphisms and DKD.

Plasma levels of miR-29b and miR-200b in type 2 diabetic retinopathy.

MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case-control study aimed to investigate whether the plasma levels of miR-29b and miR-200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non-proliferative DR and 49 with proliferative DR). We also included 20 healthy blood donors to determine the miRNA expression in the general population. Plasma levels of miR-29b and miR-200b were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferative DR was inversely associated with plasma levels of miR-29b (unadjusted OR = 0.694, 95% CI: 0.535-0.900, P = 0.006) and miR-200b (unadjusted OR = 0.797, 95% CI: 0.637-0.997, P = 0.047). However, these associations were lost after controlling for demographic and clinical covariates. In addition, patients with type 2 diabetes had lower miR-200b levels than blood donors. Our findings reinforce the importance of addressing the role of circulating miRNAs, including miR-29 and miR-200b, in DR.

Renal effects of exendin-4 in an animal model of brain death.

Organ transplantation is the gold standard therapy for the majority of patients with terminal organ failure. However, it is still a limited treatment especially due to the low number of brain death (BD) donors in relation to the number of waiting list recipients. Strategies to increase the quantity and quality of donor organs have been studied, and the administration of exendin-4 (Ex-4) to the donor may be a promising approach. Male Wistar rats were randomized into 3 groups: (1) control, without central nervous system injury; (2) BD induced experimentally, and (3) BD induced experimentally + Ex-4 administered immediately after BD induction. After BD induction, animals were monitored for 6 h before blood collection and kidney biopsy. Kidney function was assessed by biochemical quantification of plasma kidney markers. Gene and protein expressions of inflammation- and stress-related genes were evaluated by RT-qPCR and immunoblot analysis. Animals treated with Ex-4 had lower creatinine and urea levels compared with controls. BD induced oxidative stress in kidney tissue through increased expression of Ucp2, Sod2 and Inos, and Ex-4 administration reduced the expression of these genes. Ex-4 also induced increased expression of the anti-apoptotic Bcl2 gene. Nlrp3 and Tnf expressions were up-regulated in the BD group compared with controls, but Ex-4 treatment had no effect on these genes. Our findings suggest that Ex-4 administration in BD rats reduces BD-induced kidney damage by decreasing the expression of oxidative stress genes and increasing the expression of Bcl2.

The A allele of the UCP2 -866G/A polymorphism changes UCP2 promoter activity in HUVECs treated with high glucose.

The mitochondrial uncoupling protein 2 (UCP2) decreases reactive oxygen species (ROS) formation by mitochondria. Our group previously showed that the UCP2 -866A allele was associated with risk of diabetic retinopathy (DR), which is caused by hyperglycemia-induced oxidative stress. To date, it is still unclear if the -866A allele directly affects UCP2 expression in endothelial cells. Thus, we investigated the effect of the A allele on UCP2 promoter activity in HUVECs treated with high glucose (HG) or hydrogen peroxide (H2O2). To quantify UCP2 promoter activity, HUVECs were transfected with pGL3 plasmids containing the UCP2 promoter and the firefly luciferase coding sequence. Experimental groups were: (1) pGL3-866G-transfected cells and (2) pGL3-866A cells, both under normal (4 mM) or HG (25 mM) concentrations for 24 h and 48 h or incubated with H2O2 (0.1 mM) for 1 h. UCP2 promoter activity was monitored by Luminescent Dual-luciferase Assay. HG induced an upregulation of UCP2 promoter activity in PGL3-866G cells after 24 h of treatment (P = 0.027), but not after 48 h. Compared to pGL3-866G cells, pGL3-866A cells seems to have reduced UCP2 promoter activity following 24 h and 48 h of normal glucose treatment (P = 0.087 and P = 0.022). After HG treatment, pGL3-866A cells had more marked UCP2 downregulation (24 h: - 3.2-folds, P < 0.001; and 48 h: - 2.5-folds, P < 0.001 vs. G cells). Both pGL3-866G and pGL3-866A cells treated with H2O2 showed a ≅ 4-fold increase in UCP2 promoter activity (both P < 0.001). The -866A allele modifies UCP2 promoter activity in HUVECs under HG treatment but not in the H2O2 condition.

Association of -1082A>G Polymorphism in the Interleukin-10 Gene with Estimated Glomerular Filtration Rate in Type 2 Diabetes.

BACKGROUND/AIMS: The -1082A>G polymorphism (rs1800896) in the interleukin-10 (IL10) gene has been associated with type 2 diabetes and diabetic retinopathy, but its relationship with diabetic kidney disease (DKD) is uncertain. The aim of this case-control study was to investigate whether the -1082A>G polymorphism is associated with DKD in white Brazilians with type 2 diabetes mellitus. METHODS: Genotyping was done by real-time polymerase chain reaction for 597 type 2 diabetic outpatients. The definition of DKD was based on estimated glomerular filtration rate (eGFR) and albuminuria, and the patients were grouped in three categories: no DKD (n=249), mild to moderate DKD (n=222), and severe DKD (n=126). RESULTS: The frequency of the minor (G) allele in subjects without DKD did not differ from that observed in subjects with DKD (0.35 vs 0.39, respectively; P = 0.192). Genotype frequencies in subjects without DKD were not significantly different from those observed among patients with mild to moderate DKD or severe DKD. However, considering only the eGFR categories as an indicator of renal function, the AG genotype was independently associated with an increased risk of mildly to moderately decreased eGFR (G3a category) and GG genotype was independently associated with increased risk of kidney failure (G5 category) as compared with AA genotype. CONCLUSION: Our findings support the hypothesis that the -1082A>G polymorphism in the IL10 gene might be associated with DKD in white Brazilians with type 2 diabetes.

Nitric oxide levels in patients with diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Altered serum nitric oxide (NO) levels in patients with diabetes mellitus (DM) have been reported by different studies; however, results are still controversial. Until this date, no meta-analysis evaluated the association of NO levels with DM. Thus, this paper describes a meta-analysis conducted to evaluate if there is a relationship between NO levels and type 1 DM (T1DM) or type 2 DM (T2DM). METHODS: A literature search was done to identify all studies that investigated NO levels between T1DM or T2DM patients (cases) and non-diabetic subjects (controls). Measurement of nitrate and nitrite (NOx - the stable NO products) were used to estimate NO concentrations because they closely reflect NO bioavailability. Weighted mean differences (WMD) of NOx levels between case and control samples were calculated for T1DM and T2DM groups. RESULTS: Thirty studies were eligible for inclusion in the meta-analysis (8 in T1DM samples and 22 in T2DM samples). NOx levels were increased in European T1DM patients compared with controls [random effect model (REM) WMD = 8.55, 95% CI 2.88 - 14.21]. No other ethnicity was evaluated in T1DM studies. NOx levels were also increased in both European (REM WMD = 18.76, 95% CI 1.67 - 35.85) and Asian (REM WMD = 18.41, 95% CI 8.01 - 28.81) T2DM patients, but not in Latin American patients compared with controls. CONCLUSIONS: This meta-analysis detected a significant increase in NOx levels in European T1DM patients as well as European and Asian T2DM patients. Further studies in other ethnicities are necessary to confirm these data.

Exendin-4 attenuates brain death-induced liver damage in the rat.

The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates.

A high-glycemic index, low-fiber breakfast affects the postprandial plasma glucose, insulin, and ghrelin responses of patients with type 2 diabetes in a randomized clinical trial.

BACKGROUND: Meals with a low glycemic index (GI) and rich in fiber could be beneficial with regard to postprandial metabolic profile and satiety. OBJECTIVE: The aim of this study was to investigate the effect of 4 breakfasts with a different GI and amount of fiber on postprandial plasma glucose, insulin, and appetite in patients with type 2 diabetes. METHODS: This randomized 4-intervention crossover trial included 14 patients [7 men; ages 65.8 ± 5.2 y; glycated hemoglobin: 6.6 ± 0.9%; BMI (in kg/m(2)): 27.2 ± 3.1]. Dietary interventions were as follows: breakfasts with a high GI (60.4 ± 0.1%) and high fiber (6.0 ± 0.3 g) (HGI-HF), a high GI (60.9 ± 1.7%) and low fiber (2.5 ± 0.4 g) (HGI-LF), a low GI (37.7 ± 0.1%) and high fiber (6.2 ± 0.3 g) (LGI-HF), and a low GI (39.8 ± 1.3%) and low fiber (2.0 ± 0.1 g) (LGI-LF). Plasma glucose, insulin, and total ghrelin were evaluated postprandially (0-180 min). A visual analog scale was used to assess appetite. Data were analyzed by generalized estimating equations and post hoc least significant difference (LSD) tests. Data are reported as means ± SDs. RESULTS: The area under the curve (AUC) [mean (95% CI); P for LSD tests] for plasma glucose (mmol/L × min) was higher after patients consumed the HGI-LF breakfast [9.62 (8.39, 10.84)] than after the LGI-HF breakfast [8.95 (7.71, 10.18)] (P ≤ 0.05). Insulin AUC (µIU/mL × min) after patients consumed the HGI-LF meal [65.72 (38.24, 93.19)] was higher than after the HGI-HF meal [57.24 (32.44, 82.04)] (P ≤ 0.05). The other observed difference was higher insulin AUC after the consumption of the LGI-LF breakfast [61.54 (36.61, 86.48)] compared with the AUC after the LGI-HF breakfast [54.16 (31.43, 76.88)] (P ≤ 0.05). Plasma ghrelin decreased in comparison with baseline only after patients consumed the LGI-HF and LGI-LF breakfasts (P ≤ 0.05). Subjective satiety did not differ between breakfasts. CONCLUSIONS: Plasma glucose, insulin, and ghrelin responses were least favorable when patients with type 2 diabetes consumed a breakfast with a high GI and low fiber, which suggests that reducing the GI or increasing the fiber content or both of breakfasts may be a useful strategy to improve the postprandial metabolic profile of these patients. This trial was registered at clinicaltrials.gov as NCT01410292.

Association of the UCP polymorphisms with susceptibility to obesity: case-control study and meta-analysis.

This paper describes a case-control study and a meta-analysis performed to evaluate if the following polymorphisms are associated with presence of obesity: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3). The case-control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes. A literature search was made to identify all studies that evaluated associations between UCP1-3 polymorphisms and obesity. In the case-control study the distributions of the UCP variants did not differ between obese and non-obese groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and the results showed that the UCP2 -866G/A and UCP3 -55C/T polymorphisms were associated with protection to obesity in Europeans (OR = 0.89, 95% CI 0.82-0.97 and OR = 0.88, 95% CI 0.80-0.97, respectively). The UCP2 Ala55 val polymorphism was associated with obesity in Asians (OR = 1.61, 95% CI 1.13-2.30). The UCP2 Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19, 95% CI 1.00-1.42). There was no significant association of the UCP1 -3826A/G polymorphism with obesity. In our case-control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 -866G/A, Ins/Del, Ala55Val and UCP3 -55C/T polymorphisms with obesity.

Association study of sorbitol dehydrogenase -888G>C polymorphism with type 2 diabetic retinopathy in Caucasian-Brazilians.

Diabetic retinopathy (DR) is a common chronic complication of diabetes and remains the leading cause of blindness in working-aged people. Hyperglycemia increases glucose flux through the polyol pathway, in which aldose reductase converts glucose into intracellular sorbitol, which is subsequently converted to fructose by sorbitol dehydrogenase (SDH). The accelerated polyol pathway triggers a cascade of events leading to retinal vascular endothelial dysfunction and the eventual development of DR. Polymorphisms in the gene encoding aldose reductase have been consistently associated with DR. However, only two studies have analyzed the relationship between polymorphisms in the gene encoding SDH (SORD) and DR. In this case-control study, we investigated whether the -888G > C polymorphism (rs3759890) in the SORD gene is associated with the presence or severity of DR in 446 Caucasian-Brazilians with type 2 diabetes (241 subjects with and 205 subjects without DR). The -888G > C polymorphism was also examined in 105 healthy Caucasian blood donors, and the genotyping of this polymorphism was carried out by real-time PCR. The genotype and allele frequencies of the -888G > C polymorphism in patients with type 2 diabetes were similar to those of blood donors (G allele frequency = 0.16 in both groups of subjects). Similarly, the genotype and allele frequencies in patients with DR or the proliferative form of DR were similar to those of patients without this complication (P > 0.05 for all comparisons). Thus, our findings suggest that the -888G > C polymorphism in the SORD gene is not involved in the pathogenesis of DR in type 2 diabetes.

Integrated bioinformatics approach reveals methylation-regulated differentially expressed genes in obesity.

Objective: To identify DNA methylation and gene expression profiles involved in obesity by implementing an integrated bioinformatics approach. Materials and methods: Gene expression (GSE94752, GSE55200, and GSE48964) and DNA methylation (GSE67024 and GSE111632) datasets were obtained from the GEO database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in subcutaneous adipose tissue of patients with obesity were identified using GEO2R. Methylation-regulated DEGs (MeDEGs) were identified by overlapping DEGs and DMGs. The protein-protein interaction (PPI) network was constructed with the STRING database and analyzed using Cytoscape. Functional modules and hub-bottleneck genes were identified by using MCODE and CytoHubba plugins. Functional enrichment analyses were performed based on Gene Ontology terms and KEGG pathways. To prioritize and identify candidate genes for obesity, MeDEGs were compared with obesity-related genes available at the DisGeNET database. Results: A total of 54 MeDEGs were identified after overlapping the lists of significant 274 DEGs and 11,556 DMGs. Of these, 25 were hypermethylated-low expression genes and 29 were hypomethylated-high expression genes. The PPI network showed three hub-bottleneck genes (PTGS2, TNFAIP3, and FBXL20) and one functional module. The 54 MeDEGs were mainly involved in the regulation of fibroblast growth factor production, the molecular function of arachidonic acid, and ubiquitin-protein transferase activity. Data collected from DisGeNET showed that 11 of the 54 MeDEGs were involved in obesity. Conclusion: This study identifies new MeDEGs involved in obesity and assessed their related pathways and functions. These results data may provide a deeper understanding of methylation-mediated regulatory mechanisms of obesity.

Association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR in critically ill patients: A prospective cohort study.

This study aimed to investigate the association between diabetes and stress-induced hyperglycemia with skeletal muscle gene expression of INSR of critically ill patients. Skeletal muscle biopsies were prospectively taken from the vastus muscle, and the expression level of INSR was analyzed using RT-qPCR. Fifty patients were included from April 2018 to September 2018. No significant differences in skeletal muscle gene expression were found between patients with or without diabetes. Similarly, there were no differences in gene expression between groups according to the presence of hypoglycemia 〈 70 mg/dl or hyperglycemia 〉 140 mg/dl. Patients with glycemic variability ≥ 40 mg/dl exhibited a downregulation of INSR compared to those with glycemic variability < 40 mg/dl (1.3 [0.01-5] vs. 2.1 [0.7 - 3.4] fold-changes, P = 0.045). The same pattern was observed when glycemic gap threshold of 80 mg/dl was used (1.4 [0.25-5] vs 1 [0.01 - 2.3] fold-changes in patients with glycemic gap < 80 mg/dl and glycemic gap ≥ 80 mg/dl respectively, P = 0.015). In conclusion, INSR was downregulated in the skeletal muscle of critically ill patients with stress-induced hyperglycemia.