Diabetology & Metabolic Syndrome

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ISSN / EISSN : 1758-5996 / 1758-5996
Current Publisher: Springer Science and Business Media LLC (10.1186)
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Total articles ≅ 1,314
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Diabetology & Metabolic Syndrome, Volume 13, pp 1-11; doi:10.1186/s13098-021-00677-w

Background Prediabetes is characterized by a hemoglobin A1c of 5.7–6.4% and fasting blood glucose of 100–125 mg/dl. A high percentage of prediabetes subjects develop type 2 diabetes mellitus in the next years. The effects of opioid peptides and their receptors, in addition to immunological cytokines, on prediabetes are not well understood. Therefore, molecular, physiological, and clinical studies are required to link the opioid system, immune system, and insulin resistance (IR) in prediabetes. We hypothesize that opioid peptides (endomorphin-2 (EM2), and β-endorphin (βEP)), and their receptors (µ-opioid receptors (MOR) and κ-opioid receptors (KOR)), in addition to the inflammatory cytokines (IL-6) and anti-inflammatory cytokine (IL-10), affect IR parameters in patients with prediabetes. Methods Sixty prediabetes patients with IR (prediabetes+IR) and sixty prediabetes patients without IR (prediabetes-IR), in addition to 58 controls, have participated in the study. IL-6, IL-10, EM2, βEP, MOR, and KOR were measured by the ELISA technique. Results In general, most prediabetes subjects have dyslipidemia. The IL-6, IL-10, β-endorphin, MOR, and endomorphin-2 were higher in the prediabetes subgroups than the control group. The immune system was activated in the prediabetes in an IR-dependent manner. Prediabetes+IR can be predicted by the increased levels of IL-10, βEP, and EM2 and by the combination of IL-10 and EM2/KOR with good sensitivity and specificity. Conclusion Opioid peptides and their receptors were upregulated in patients with prediabetes, depending on the significance of IR and the immune cytokines. The intercorrelation between the immune system, EOS, and insulin in prediabetes was confirmed.
Hye Yoon Jang, Youngmin Han, Hye Jin Yoo, Jong Ho Lee,
Diabetology & Metabolic Syndrome, Volume 13, pp 1-10; doi:10.1186/s13098-021-00679-8

Background Research elucidating the metabolic mechanisms that differentiate subtypes of obesity has been increasing. We aimed to investigate the effects of a 12-week dietary intervention on the metabolomic profiles of obese subjects. Methods Subjects followed a 12-week dietary restriction protocol consisting of a 300 kcal/day reduction in their usual caloric intake. Twenty-nine obese subjects were included and divided into two groups: the metabolic status maintenance group (n = 17, controls) and the metabolic status improvement group (n = 12, tests). We analyzed the somatometric and biochemical parameters and performed ultra-performance liquid chromatography-mass spectrometry analysis of the plasma metabolites. Results At 12 weeks, the fat percentage, whole fat area (WFA), subcutaneous fat area (SFA) at the L1 vertebra, and the levels of triglycerides, gamma-glutamyltransferase (gamma-GT), and leptin were markedly decreased in the metabolic status improvement group, while the level of high-density lipoprotein cholesterol increased compared with that in the metabolic status maintenance group. Metabolomic profiling at 12 weeks showed substantial differences in 4-aminobutyraldehyde (p = 0.005) and 4’-apo-β-carotenal (p = 0.024) between the two groups. Furthermore, an AUC value of 0.89 was obtained for the following seven featured biomarkers: triglycerides, gamma-GT, leptin, fat percentage, WFA, and SFA at the L1 vertebra, and 4-aminobutyraldehyde. Conclusions We demonstrated that 4-aminobutyraldehyde and related regional fat distribution parameters were strongly associated with obesity according to metabolic status. Thus, these biomarkers are potentially valuable in confirming the efficacy of short-term interventions and predicting metabolic status in obese individuals. Trials registration: This study was registered at ClinicalTrials.gov under NCT03135132 (registered 1 May 2017—retrospectively registered).
, Yücel Arman, Şengül Aydın Yoldemir, Ayşe Selcen Pala, Perihan Özkan Gümüşkaya, Mustafa Özcan, Mustafa Karataş, Okan Dikker, Tufan Tükek
Diabetology & Metabolic Syndrome, Volume 13, pp 1-7; doi:10.1186/s13098-021-00682-z

Background Laminin, one of the largest glycoproteins of the basement membrane, is an important component of the extracellular matrix. Functions of the basement membrane include regulation of cell signaling behaviors and structural support. Laminin plays a critical role in the regulation of insulin action in muscle, liver, and adipose tissue. The study mainly investigates an association between the change in serum laminin levels and insulin resistance and non-alcoholic hepatosteatosis. Methods This prospective study included a total of 90 participants; 60 patients diagnosed with Grade 2–3 non-alcoholic hepatosteatosis and 30 age- and sex-matched healthy controls between December 2019 and December 2020. Routine laboratory tests including glucose, insulin, homeostatic model of assessment-insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and C-reactive protein and laminin levels were measured in the serum of the patient and control groups. Enzyme-linked immunosorbent assay was used for the measurement of laminin levels. Results The median serum laminin levels were lower in patients with hepatic steatosis, compared to the control group (72 ng/L vs. 82 ng/L, respectively; p = 0.003). In the patients with insulin resistance, median laminin levels were lower, regardless of the presence of non-alcoholic hepatosteatosis (67 ng/L vs. 85 ng/L, respectively; p = 0.007). There was a weak, negative correlation between the laminin levels and HOMA-IR. Conclusions Our study results suggest that, although there is no exact link between laminin and non-alcoholic hepatosteatosis, serum laminin levels are lower in patients with insulin resistance by regulating the insulin effect through integrins.
Li Zhang, Ming Zeng, Fei Tang, Jun Chen, Dongmei Cao, Ze-Nan Tang
Diabetology & Metabolic Syndrome, Volume 13, pp 1-14; doi:10.1186/s13098-021-00678-9

Background Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. CircRNA polyribonucleotide nucleotidyltransferase 1 (circ-PNPT1) has been found to be abnormally expressed in GDM patients. However, function and mechanism of circ-PNPT1 in GDM remain largely undefined. Methods Levels of circ-PNPT1, microRNA (miR)-889-3p and PAK1 (p21 (RAC1) activated kinase 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry, transwell and wound healing assays, respectively. The binding interaction between miR-889-3p and circ-PNPT1 or PAK1 was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy (TEM). Results Circ-PNPT1 was highly expressed in the placental tissues of GDM and high glucose (HG)-induced trophoblast cells. Knockdown of circ-PNPT1 reversed HG-induced arrest of trophoblast cell viability, migration, invasion and the promotion of cell apoptosis. Mechanistically, we confirmed circ-PNPT1 could promote the expression of PAK1, the target of miR-889-3p, by directly sponging miR-889-3p, and circ-PNPT1 regulated HG-induced trophoblast cell dysfunction by miR-889-3p/PAK1 axis. Further studies showed circ-PNPT1 was packaged into exosomes and could be internalized by surrounding trophoblast cells. Conclusion Circ-PNPT1 promoted HG-induced trophoblast cell biological dysfunction through miR-889-3p/PAK1 axis. Meanwhile, it could be transferred from HG-induced trophoblast cells to surrounding untreated cells via exosomes.
Jia Y. Wan, Deborah L. Goodman, Emileigh L. Willems, Alexis R. Freedland, Trina M. Norden-Krichmar, Stephanie A. Santorico, Karen L. Edwards, Eric Boerwinkle, John Buse, Ralph DeFronzo, et al.
Diabetology & Metabolic Syndrome, Volume 13, pp 1-15; doi:10.1186/s13098-021-00670-3

Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects. Conclusions This multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.
Hamideh Dinari Ghozhdi, , Maryam Keshvari, Hassan Tavassoli
Diabetology & Metabolic Syndrome, Volume 13, pp 1-10; doi:10.1186/s13098-021-00676-x

Background Adipocytokines, which are secreted by the adipose tissue, contribute to the pathogenesis of obesity-related complications. To evaluate this assumption, we investigated the effects of aerobic exercise training (AET), resistance exercise training (RET), and 4 weeks of de-training on serum leptin and TNF-α levels in diabetic rats. Method 36 Wistar rats were divided into normal diet (ND) (control, RET, AET) and high-fat diet (HFD) + STZ (control, RET, AET) groups. Serum insulin, leptin, and TNF-α levels were assessed by commercial ELISA kits. Also fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) levels were measured by the colorimetric kits. Results Diabetes induction increased body weight (BW) and FBG, and decreased insulin compared to the ND rats’ groups (p < 0.001). 12-weeks of AET and RET programs in the trained diabetic rats led to a decrease in TG, LDL-C, leptin, TNF-α, and FBG, and an increase in insulin compared to the HFD + STZ-C group (p < 0.001). Besides, there was no difference between AET and RET in improving the variables studied (p > 0.05). Also, de-training led to increased BW, TG, leptin, and TNF-α compared to the end of the exercise training (p < 0.05). The correlation between the variables studied was established at different stages of the study (p < 0.05), and only BW was not correlated with insulin during exercise training and de-training (p > 0.05). Conclusion These findings indicate that both AET and RET are useful in reducing levels of serum adipocytokines (TNF-α, leptin) in diabetic and non-diabetic rats. At the same time, 4 weeks of de-training was sufficient to lose the metabolic adaptations.
Diabetology & Metabolic Syndrome, Volume 13, pp 1-15; doi:10.1186/s13098-021-00672-1

Background Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2). Methods DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. Results Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R 2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. Conclusions This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. Trial registration: ISRCTN53984585
, Silvia Selinski, Christina Bächle, Joachim Rosenbauer
Diabetology & Metabolic Syndrome, Volume 13, pp 1-7; doi:10.1186/s13098-021-00673-0

Background This study aims to analyze the patient-reported outcome (PRO) of treatment satisfaction in a sample of children, adolescents and young adults with long-duration type 1 diabetes and to determine potential risk factors for poor treatment satisfaction and the intraindividual changes over a 3-year period. Methods This study used data from two population-based questionnaire surveys conducted in 2015–2016 and 2018–2019. The participants were 11 to 27 years old and had a type 1 diabetes duration of 10 years or longer in 2015–2016 (n = 575). Factors that were potentially associated with poor treatment satisfaction (moderate, poor or very poor) compared to the reference group (very good or good treatment satisfaction) were analyzed by log binomial regression adjusted for sex and age group. Results In 2015–2016 (2018–2019), 26% (33%) of the respondents rated their diabetes treatment/consultation as "very good", 53% (46%) as "good", and 20% (21%) as "poor". Based on the 2018–2019 data, girls/women had an increased risk of poor treatment satisfaction (RRgirls/women: 1.64 (1.10; 2.44), p = 0.016). In addition, people with hemoglobin A1c (HbA1c) values ≥ 7.5% had a more than twice the risk of poor treatment satisfaction than people with HbA1c values < 7.5% (RRHbA1c ≥7.5%: 2.43 (1.63; 3.63), p < 0.001). A total of 42% of people with poor treatment satisfaction in 2015–2016 also reported poor treatment satisfaction at follow-up. Conclusions Most study participants were satisfied with their diabetes treatment. However, we identified risk groups that would benefit from targeted interventions to improve this important PRO.
Jie Cao, Hong Wang, , Xue-Qin Wang, Dong-Mei Zhang, Xiao-Hua Wang, Wang-Shu Liu, Xiao-Qin Ge
Diabetology & Metabolic Syndrome, Volume 13, pp 1-8; doi:10.1186/s13098-021-00671-2

Objective Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease, which characterized by islet beta cell dysfunction. Serum adenosine deaminase (ADA) is an important enzyme that regulates the biological activity of insulin, and its levels are greatly increased in inflammatory diseases with insulin resistance. The present study was designed to explore the relationship between serum ADA levels and islet beta cell function in patients with T2D. Methods This cross-sectional study recruited 1573 patients with T2D from the Endocrinology Department of the Affiliated Hospital 2 of Nantong University between 2015 and 2018. All participants were received serum ADA test and oral glucose tolerance test (OGTT). Insulin sensitivity index (assessed by Matsuda index using C-peptide, ISIM-cp), insulin secretion index (assessed by ratio of area under the C-peptide curve to glucose curve, AUCcp/glu) and islet beta cell function (assessed by insulin secretion-sensitivity index 2 using C-peptide, ISSI2cp) were derived from OGTT. And other clinical parameters, such as HbA1c, were also collected. Results It was showed that HbA1c was significantly increased, while ISIM-cp, AUCcp/glu and ISSI2cp significantly decreased, across ascending quartiles of serum ADA levels. Moreover, serum ADA levels were negatively correlated with ISSI2cp (r = − 0.267, p < 0.001). Furthermore, after adjusting for other clinical parameters by multiple linear regression analysis, serum ADA levels were still independently associated with ISSI2cp (β = − 0.125, t = − 5.397, p < 0.001, adjusted R 2 = 0.459). Conclusions Serum ADA levels are independently associated with islet beta cell function in patients with T2D.
Ebrahim Mokhtari, Hossein Farhadnejad, , , Fereidoun Azizi
Diabetology & Metabolic Syndrome, Volume 13, pp 1-11; doi:10.1186/s13098-021-00674-z

Background We aim to assess the association of empirical dietary (EDIH) and lifestyle (ELIH) index for hyperinsulinemia with the risk of insulin resistance, hyperinsulinemia, insulin sensitivity, and β-cell dysfunction in Iranian adults. Methods In this prospective study, a total of 1244 men and women aged ≥ 20 years were selected among participants of the Tehran lipid and glucose study and followed for 3.2 years. Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle insulinemic potential indices were calculated using dietary intake, body mass index, and physical activity information. Multivariable logistic regression was used to estimate the associated risk of a 3-year incidence of insulin-related disorders. Results The mean ± SD age and BMI of all eligible participants (42.7% males) were 43.0 ± 13.0 and 27.4 ± 4.9 in the study's baseline. After adjusting for all potential confounders, participants in the highest tertile of ELIH score had a greater risk of developing hyperinsulinemia (OR:2.42, 95%CI:1.52–3.86, P for trend = < 0.001), insulin resistance (OR:2.71, 95%CI:1.75–4.18, P for trend = < 0.001) and insulin insensitivity (OR:2.65, 95%CI: 1.72–4.10, P for trend = < 0.001) compared with those in the lowest tertile. However, the risk of incident β-cell dysfunction was lower in individuals with a higher score of ELIH in comparison to those with the lowest score (OR:0.30, 95%CI:0.19–0.45, P for trend = < 0.001). Conclusions Empirical lifestyle index for hyperinsulinemia was directly associated with insulin resistance, insulin insensitivity, and hyperinsulinemia and was inversely associated with β-cells dysfunction.
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