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11 pages, 1015 KiB

Open AccessArticle

Circadian Patterns of Patients with Type 2 Diabetes and Obstructive Sleep Apnea

by Trinitat Cambras, Odile Romero, Antoni Díez-Noguera, Albert Lecube and Gabriel Sampol

J. Clin. Med. 2021, 10(2), 244; https://doi.org/10.3390/jcm10020244 - 11 Jan 2021

Cited by 3 | Viewed by 2031

Abstract

Sleep apnea, a condition that modifies sleep and circadian rhythms, is highly prevalent in patients with diabetes. However, it is not known if there is an association between sleep apnea, circadian alterations and glycemic regulation in this type of patient. Here, a polysomnographic [...] Read more.

Sleep apnea, a condition that modifies sleep and circadian rhythms, is highly prevalent in patients with diabetes. However, it is not known if there is an association between sleep apnea, circadian alterations and glycemic regulation in this type of patient. Here, a polysomnographic study was carried out on 21 women and 25 men (mean age = 64.3 ± 1.46 years) with diagnoses of type 2 diabetes to detect the presence of sleep apnea. Moreover, patients wore an actigraph and a temperature sensor on the wrist for one week, to study the manifestation of the circadian rhythms. The correlations of circadian and polysomnographic variables with the severity of apnea, measured by the apnea-hypopnea index, and with glycemic dysregulation, measured by the percentage of glycated hemoglobin, were analyzed. The mean apnea-hypoapnea index of all the participants was 39.6 ± 4.3. Apnea-hypoapnea index correlated with % N1, negatively with % N3, and also the stability of the active circadian rhythm. However, no significant correlation was found between the apnea-hypopnea index and wrist temperature rhythm and glycated hemoglobin. Glycated hemoglobin levels were negatively associated with the percentage of variance explained by the wrist temperature circadian rhythm (calculated via 24 and 12 h rhythms). This association was independent of body mass index and was strongest in patients with severe apnea. In conclusion, patients with diabetes showed altered circadian rhythms associated with a poor glycemic control and this association could partially be related to the coexistence of sleep apnea. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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11 pages, 283 KiB

Open AccessArticle

Acute Effects of Metformin and Vildagliptin after a Lipid-Rich Meal on Postprandial Microvascular Reactivity in Patients with Type 2 Diabetes and Obesity: A Randomized Trial

by Alessandra Schiappacassa, Priscila A. Maranhão, Maria das Graças Coelho de Souza, Diogo G. Panazzolo, José Firmino Nogueira Neto, Eliete Bouskela and Luiz Guilherme Kraemer-Aguiar

J. Clin. Med. 2020, 9(10), 3228; https://doi.org/10.3390/jcm9103228 - 9 Oct 2020

Cited by 5 | Viewed by 2191

Abstract

Background: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action [...] Read more.

Background: Type 2 diabetes mellitus and obesity are both related to endothelial dysfunction. Postprandial lipemia is a cardiovascular risk. Notably, it is known that a high-fat diet may elicit microvascular dysfunction, even in healthy subjects. Since anti-diabetic drugs have different mechanisms of action and also distinct vascular benefits, we aimed to compare the results of two anti-diabetic drugs after the intake of a lipid-rich meal on microcirculation in patients with type 2 diabetes and obesity. In parallel, we also investigated the metabolic profile, oxidative stress, inflammation, plasma viscosity, and some gastrointestinal peptides. Subjects/Methods: We included 38 drug-naïve patients, all women aged between 19 and 50 years, with BMI ≥ 30 kg/m². We performed endothelial measurements and collected samples before (fasting) and after the intake of a lipid-rich meal at 30, 60, 120, and 180 min. Patients were randomized to metformin or vildagliptin, given orally just before the meal. Endothelial function was assessed by videocapillaroscopy and laser-Doppler flowmetry to investigate microvascular reactivity. Besides, we also investigated plasma viscosity, inflammatory and oxidative stress biomarkers, gastrointestinal peptides, and metabolic profile in all time points. Results: No differences at baseline were noted between groups. Vildagliptin increased glucagon-like peptide-1 compared to metformin. Paired comparisons showed that, during the postprandial period, vildagliptin significantly changed levels of insulin and glucagon-like peptide-1, and also the dipeptidyl peptidase-4 activity, while metformin had effects on plasma glucose solely. Metformin use during the test meal promoted an increase in functional capillary density, while vildagliptin kept non-nutritive microvascular blood flow and vasomotion unchanged. Conclusions: After the intake of a lipid-rich meal, the use of vildagliptin preserved postprandial non-nutritive microflow and vasomotion, while metformin increased capillary recruitment, suggesting protective and different mechanisms of action on microcirculation. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

13 pages, 677 KiB

Open AccessArticle

Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population

by Sara Sokooti, Lyanne M. Kieneker, Martin H. de Borst, Anneke Muller Kobold, Jenny E. Kootstra-Ros, Jolein Gloerich, Alain J. van Gool, Hiddo J. Lambers Heerspink, Ron T Gansevoort, Robin P.F. Dullaart and Stephan J. L. Bakker

J. Clin. Med. 2020, 9(9), 3001; https://doi.org/10.3390/jcm9093001 - 17 Sep 2020

Cited by 18 | Viewed by 4751

Abstract

C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and [...] Read more.

C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes independent of glucose and insulin levels and to examine potential effect-modification by variables related to kidney function. We included 5176 subjects of the Prevention of Renal and Vascular End-Stage Disease study without type 2 diabetes at baseline. C-peptide was measured in plasma with an electrochemiluminescent immunoassay. Cox proportional hazards regression was used to evaluate the association between C-peptide level and type 2 diabetes development. Median C-peptide was 722 (566–935) pmol/L. During a median follow-up of 7.2 (6.0–7.7) years, 289 individuals developed type 2 diabetes. In multivariable-adjusted Cox regression models, we observed a significant positive association of C-peptide with the risk of type 2 diabetes independent of glucose and insulin levels (hazard ratio (HR): 2.35; 95% confidence interval (CI): 1.49–3.70). Moreover, we found significant effect modification by hypertension and albuminuria (p < 0.001 and p = 0.001 for interaction, respectively), with a stronger association in normotensive and normo-albuminuric subjects and absence of an association in subjects with hypertension or albuminuria. In this population-based cohort, elevated C-peptide levels are associated with an increased risk of type 2 diabetes independent of glucose, insulin levels, and clinical risk factors. Elevated C-peptide level was not independently associated with an increased risk of type 2 diabetes in individuals with hypertension or albuminuria. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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10 pages, 661 KiB

Open AccessArticle

Clinical Applicability of the Specific Risk Score of Dementia in Type 2 Diabetes in the Identification of Patients with Early Cognitive Impairment: Results of the MOPEAD Study in Spain

by Angel Michael Ortiz Zuñiga, Rafael Simó, Octavio Rodriguez-Gómez, Cristina Hernández, Adrian Rodrigo, Laura Jamilis, Laura Campo, Montserrat Alegret, Merce Boada and Andreea Ciudin

J. Clin. Med. 2020, 9(9), 2726; https://doi.org/10.3390/jcm9092726 - 24 Aug 2020

Cited by 8 | Viewed by 3378

Abstract

Introduction: Although the Diabetes Specific Dementia Risk Score (DSDRS) was proposed for predicting risk of dementia at 10 years, its usefulness as a screening tool is unknown. For this purpose, the European consortium MOPEAD included the DSDRS within the specific strategy for screening [...] Read more.

Introduction: Although the Diabetes Specific Dementia Risk Score (DSDRS) was proposed for predicting risk of dementia at 10 years, its usefulness as a screening tool is unknown. For this purpose, the European consortium MOPEAD included the DSDRS within the specific strategy for screening of cognitive impairment in type 2 diabetes (T2D) patients attended in a third-level hospital. Material and Methods: T2D patients > 65 years, without known cognitive impairment, attended in a third-level hospital, were evaluated. As per MOPEAD protocol, patients with MMSE ≤ 27 or DSDRS ≥ 7 were referred to the memory clinic for complete neuropsychological assessment. Results: 112 T2D patients were recruited. A total of 82 fulfilled the criteria for referral to the memory unit (43 of them declined referral: 48.8% for associated comorbidities, 37.2% lack of interest, 13.95% lack of social support). At the Fundació ACE’s Memory Clinic, 34 cases (87.2%) of mild cognitive impairment (MCI) and 3 cases (7.7%) of dementia were diagnosed. The predictive value of DSDRS ≥ 7 as a screening tool of cognitive impairment was AUROC = 0.739, p 0.024, CI 95% (0.609–0.825). Conclusions: We found a high prevalence of unknown cognitive impairment in TD2 patients who attended a third-level hospital. The DSDRS was found to be a useful screening tool. The presence of associated comorbidities was the main factor of declining referral. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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10 pages, 1304 KiB

Open AccessArticle

Effect of Type 2 Diabetes Mellitus on the Hypoxia-Inducible Factor 1-Alpha Expression. Is There a Relationship with the Clock Genes?

by Carolina López-Cano, Liliana Gutiérrez-Carrasquilla, Ferran Barbé, Enric Sánchez, Marta Hernández, Raquel Martí, Vicky Ceperuelo-Mallafre, Mireia Dalmases, Sonia Fernández-Veledo, Joan Vendrell, Cristina Hernández, Rafael Simó and Albert Lecube

J. Clin. Med. 2020, 9(8), 2632; https://doi.org/10.3390/jcm9082632 - 13 Aug 2020

Cited by 6 | Viewed by 2826

Abstract

Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α relates to changes in the expression of clock genes (Period homolog proteins (PER)1, [...] Read more.

Limited reports exist on the relationships between regulation of oxygen homeostasis and circadian clock genes in type 2 diabetes. We examined whether the expression of Hypoxia-Inducible Factor-1α (HIF-1α) and HIF-2α relates to changes in the expression of clock genes (Period homolog proteins (PER)1, PER2, PER3, Retinoid-related orphan receptor alpha (RORA), Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), Circadian locomotor output cycles kaput (CLOCK), and Cryptochrome proteins (CRY) 1 and CRY2) in patients with type 2 diabetes. A total of 129 subjects were evaluated in this cross-sectional study (48% with diabetes). The gene expression was measured by polymerase chain reaction. The lactate and pyruvate levels were used as surrogate of the hypoxia induced anaerobic glycolysis activity. Patients with diabetes showed an increased plasma concentration of both lactate (2102.1 ± 688.2 vs. 1730.4 ± 694.4 uM/L, p = 0.013) and pyruvate (61.9 ± 25.6 vs. 50.3 ± 23.1 uM/L, p = 0.026) in comparison to controls. However, this finding was accompanied by a blunted HIF-1α expression (1.1 (0.2 to 5.0) vs. 1.7 (0.4 to 9.2) arbitrary units (AU), p ≤ 0.001). Patients with diabetes also showed a significant reduction of all assessed clock genes’ expression. Univariate analysis showed that HIF-1α and almost all clock genes were significantly and negatively correlated with HbA1c concentration. In addition, positive correlations between HIF-1α and the clock genes were observed. The stepwise multivariate regression analysis showed that HbA1c and clock genes independently predicted the expression of HIF-1α. Type 2 diabetes modifies the expression of HIF-1α and clock genes, which correlates with the degree of metabolic control. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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18 pages, 4730 KiB

Open AccessArticle

Effect of Topical Administration of Somatostatin on Retinal Inflammation and Neurodegeneration in an Experimental Model of Diabetes

by Cristina Hernández, Ana I Arroba, Patricia Bogdanov, Hugo Ramos, Olga Simó-Servat, Rafael Simó and Angela M Valverde

J. Clin. Med. 2020, 9(8), 2579; https://doi.org/10.3390/jcm9082579 - 10 Aug 2020

Cited by 23 | Viewed by 3155

Abstract

Somatostatin (SST) is a neuroprotective peptide but little is known regarding the potential role of its anti-inflammatory effects on retinal neuroprotection. In a previous study, we provided the first evidence that topical (eye drops) administration of SST prevents retinal neurodegeneration in streptozotocin (STZ)-induced [...] Read more.

Somatostatin (SST) is a neuroprotective peptide but little is known regarding the potential role of its anti-inflammatory effects on retinal neuroprotection. In a previous study, we provided the first evidence that topical (eye drops) administration of SST prevents retinal neurodegeneration in streptozotocin (STZ)-induced diabetic rats. However, STZ by itself could cause neurotoxicity, thus acting as a confounding factor. The aims of the present study were: (1) to test the effect of topical administration of SST in the db/db mouse model, a spontaneous model of type 2 diabetes, thus avoiding the confounding effect of STZ on neurodegeneration; (2) to further explore the anti-inflammatory mechanisms of SST in glial cells. This task was performed by using mouse retinal explants and cell cultures. In summary, we confirm that SST topically administered was able to prevent retinal neurodysfunction and neurodegeneration in db/db mice. Furthermore, we found that SST prevented the activation of the classical M1 response of Bv.2 microglial cells upon Lipopolysaccharide (LPS) stimulation as a potent pro-inflammatory trigger. The anti-inflammatory effect of SST in Bv.2 cells was also observed in response to hypoxia. In conclusion, we provide evidence that the neuroprotective effect of SST in diabetic retinas can be largely attributed to anti-inflammatory mechanisms. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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18 pages, 961 KiB

Open AccessArticle

Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study

by Juan J. Gorgojo-Martínez, Manuel A. Gargallo-Fernández, Alba Galdón Sanz-Pastor, Teresa Antón-Bravo, Miguel Brito-Sanfiel and Jaime Wong-Cruz

J. Clin. Med. 2020, 9(7), 2275; https://doi.org/10.3390/jcm9072275 - 17 Jul 2020

Cited by 7 | Viewed by 4248

Abstract

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor [...] Read more.

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium–glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included—279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (−0.90%) and weight (−4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (−0.35%) and weight (−2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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12 pages, 948 KiB

Open AccessArticle

Artificial Saliva in Diabetic Xerostomia (ASDIX): Double Blind Trial of Aldiamed^® Versus Placebo

by Bruna Sinjari, Beatrice Feragalli, Umberto Cornelli, Giovanni Belcaro, Ester Vitacolonna, Manlio Santilli, Imena Rexhepi, Gianmaria D’Addazio, Francesca Zuccari and Sergio Caputi

J. Clin. Med. 2020, 9(7), 2196; https://doi.org/10.3390/jcm9072196 - 11 Jul 2020

Cited by 18 | Viewed by 4124

Abstract

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed^® spray) in comparison to a placebo spray were used to evaluate the xerostomia [...] Read more.

Xerostomia is a symptom frequently present in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In the present trial, the activity of an artificial saliva (aldiamed^® spray) in comparison to a placebo spray were used to evaluate the xerostomia and the saliva antioxidant capacity (SAT). Sixty patients of both genders with T1DM or T2DM were randomized into two groups of 30 subjects each. The experiment was a double-blind study approved by the Ethics Committee of the “G. d’Annunzio University” of Chieti and Pescara. Moreover, measurements of the stimulated saliva flow rate and the ultrasonography of the submandibular and parotid glands were performed at both the study time points. The results demonstrated statistically significant differences between the treatments in terms of the xerostomia average score. Specifically, the values were at baseline and after 30 days 2.9 ± 1.31 and 3.0 ± 1.44 and 1.4 ± 1.48 and 2.4 ± 0.99 for aldiamed^® spray and the placebo, respectively. Meanwhile, no statistically significant differences were shown between the two groups for the other variables, such as the salivary flow rate, the antioxidant capacity of the saliva, and the ultrasonography of the major salivary glands. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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11 pages, 284 KiB

Open AccessArticle

Prediabetes Is Independently Associated with Subclinical Carotid Atherosclerosis: An Observational Study in a Non-Urban Mediterranean Population

by Maria Belén Vilanova, Josep Franch-Nadal, Mireia Falguera, Josep Ramon Marsal, Sílvia Canivell, Esther Rubinat, Neus Miró, Àngels Molló, Manel Mata-Cases, Mònica Gratacòs, Esmeralda Castelblanco and Dídac Mauricio

J. Clin. Med. 2020, 9(7), 2139; https://doi.org/10.3390/jcm9072139 - 7 Jul 2020

Cited by 8 | Viewed by 2357

Abstract

This was a prospective, observational study to compare the burden of subclinical atherosclerosis as measured by carotid ultrasonography in a cohort of subjects with prediabetes vs. subjects with normal glucose tolerance (NGT) from a non-urban Mediterranean population. Atherosclerosis was assessed through carotid intima-media [...] Read more.

This was a prospective, observational study to compare the burden of subclinical atherosclerosis as measured by carotid ultrasonography in a cohort of subjects with prediabetes vs. subjects with normal glucose tolerance (NGT) from a non-urban Mediterranean population. Atherosclerosis was assessed through carotid intima-media thickness (c-IMT), the presence/absence of carotid plaques, and plaque number. Among 550 subjects included, 224 (40.7%) had prediabetes. The mean c-IMT and the prevalence of carotid plaque were significantly higher in the prediabetes group compared to the NGT group (0.72 vs. 0.67 mm, p < 0.001; and 37.9% vs. 19.6%; p < 0.001, respectively). Older age, male gender, and increased systolic blood pressure were positively correlated with c-IMT and were independent predictors of the presence of plaques. In contrast, prediabetes and low-density lipoprotein (LDL)-c were predictors of the presence of plaque (odds ratio [OR] = 1.64; 95% confidence interval [CI] = 1.05–2.57; p = 0.03 and OR = 1.01; 95% CI = 1.00–1.02; p = 0.006, respectively) together with tobacco exposure and the leukocyte count (OR = 1.77; 95% CI = 1.08–2.89; p = 0.023 and OR = 1.20; 95% CI = 1.05–1.38; p = 0.008, respectively). In a non-urban Mediterranean population, prediabetes was associated with established subclinical carotid atherosclerosis. These findings could have implications for the prevention and treatment of CV risk in these subjects before the first symptoms of cardiovascular disease appear. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

17 pages, 456 KiB

Open AccessArticle

Walking Speed is the Sole Determinant Criterion of Sarcopenia of Mild Cognitive Impairment in Japanese Elderly Patients with Type 2 Diabetes Mellitus

by Noritaka Machii, Akihiro Kudo, Haruka Saito, Hayato Tanabe, Mariko Iwasaki, Hiroyuki Hirai, Hiroaki Masuzaki and Michio Shimabukuro

J. Clin. Med. 2020, 9(7), 2133; https://doi.org/10.3390/jcm9072133 - 6 Jul 2020

Cited by 16 | Viewed by 3631

Abstract

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes [...] Read more.

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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12 pages, 1031 KiB

Open AccessArticle

Factors Associated with Risk of Diabetic Complications in Novel Cluster-Based Diabetes Subgroups: A Japanese Retrospective Cohort Study

by Hayato Tanabe, Haruka Saito, Akihiro Kudo, Noritaka Machii, Hiroyuki Hirai, Gulinu Maimaituxun, Kenichi Tanaka, Hiroaki Masuzaki, Tsuyoshi Watanabe, Koichi Asahi, Junichiro Kazama and Michio Shimabukuro

J. Clin. Med. 2020, 9(7), 2083; https://doi.org/10.3390/jcm9072083 - 2 Jul 2020

Cited by 68 | Viewed by 7589

Abstract

Diabetes is a complex and heterogeneous disease, making the prediction of the risks of diabetic complications challenging. Novel adult-onset diabetes subgroups have been studied using cluster analysis, but its application in East Asians remains unclear. We conducted a retrospective cohort study to elucidate [...] Read more.

Diabetes is a complex and heterogeneous disease, making the prediction of the risks of diabetic complications challenging. Novel adult-onset diabetes subgroups have been studied using cluster analysis, but its application in East Asians remains unclear. We conducted a retrospective cohort study to elucidate the clinical utility of cluster-based subgroup analysis in the Japanese population. Cluster analysis based on anti-glutamate decarboxylase antibody (GAD antibody) levels, age at diagnosis, body mass index (BMI), hemoglobin A1c (A1c), and homeostatic model assessment 2 estimates of β-cell function and insulin resistance was performed in 1520 diabetic patients. The risk of developing diabetic complications was analyzed using Kaplan–Meier analysis and the Cox proportional hazards model. By cluster analysis, we identified five distinct subgroups of adult-onset diabetes in the Japanese population. The risk of diabetic complications varied greatly among the clusters. Patients with severe autoimmune diabetes or severe insulin deficiency diabetes were at an increased risk of diabetic retinopathy, and those with severe insulin resistant diabetes (SIRD) had the highest risk of developing diabetic kidney disease (DKD). After adjusting for uncorrectable and correctable risk factors, SIRD was found to be an independent risk factor for DKD. In conclusion, we identified five subgroups of adult-onset diabetes and the risk factors for diabetic complications in the Japanese population. This new classification system can be effective in predicting the risk of diabetic complications and for providing optimal treatment. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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16 pages, 1771 KiB

Open AccessArticle

Role of Advanced Glycation End Products on Aortic Calcification in Patients with Type 2 Diabetes Mellitus

by Pilar Sanchis, Rosmeri Rivera, Regina Fortuny, Carlos Río, Miguel Mas-Gelabert, Marta Gonzalez-Freire, Felix Grases and Luis Masmiquel

J. Clin. Med. 2020, 9(6), 1751; https://doi.org/10.3390/jcm9061751 - 5 Jun 2020

Cited by 9 | Viewed by 2960

Abstract

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study. One-hundred and four consecutive patients [...] Read more.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify abdominal aortic calcification (AAC). Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher numbers of diabetic-related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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12 pages, 773 KiB

Open AccessArticle

The Circulating Fatty Acid Transporter Soluble CD36 Is Not Associated with Carotid Atherosclerosis in Subjects with Type 1 and Type 2 Diabetes Mellitus

by Esmeralda Castelblanco, Lucía Sanjurjo, Maria Barranco-Altirriba, Mireia Falguera, Marta Hernández, Berta Soldevila, Maria-Rosa Sarrias, Josep Franch-Nadal, Juan Antonio Arroyo, José-Manuel Fernandez-Real, Nuria Alonso and Didac Mauricio

J. Clin. Med. 2020, 9(6), 1700; https://doi.org/10.3390/jcm9061700 - 2 Jun 2020

Cited by 4 | Viewed by 2621

Abstract

This study aimed to determine the association of fatty acid transporter plasma soluble cluster of differentiation 36 (sCD36) with subclinical carotid atherosclerosis (SCA). A cross-sectional study was conducted in 1023 subjects, 225 with type 1 diabetes (T1D), 276 with type 2 diabetes (T2D) [...] Read more.

This study aimed to determine the association of fatty acid transporter plasma soluble cluster of differentiation 36 (sCD36) with subclinical carotid atherosclerosis (SCA). A cross-sectional study was conducted in 1023 subjects, 225 with type 1 diabetes (T1D), 276 with type 2 diabetes (T2D) and 522 who were nondiabetic. Carotid atherosclerotic plaque (CAP) presence was determined using B-mode carotid ultrasound imaging. sCD36 were analysed by ELISA, and CD36 surface receptor and mRNA expression were measured by flow cytometry and real-time PCR. Logistic regression models were used to evaluate sCD36 as a biomarker of SCA. Up to 376 (36.75%) participants had at least one CAP, 76 T1D, 164 T2D and 136 without diabetes, while the remaining 647 (63.25%) did not have any CAP. There were no differences in sCD36 between patients with and without CAP in T1D (p = 0.287) or T2D (p = 0.513). Although nondiabetic subjects with plaques had lower sCD36 levels than those without (p = 0.023), the multivariate models revealed no association of sCD36 with CAP in any of the three study groups. No differences were found in surface CD36 or CD36 mRNA expression between the patients with and without CAP. sCD36 is not associated with SCA in type 1 or type 2 diabetic or in nondiabetic subjects. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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18 pages, 2520 KiB

Open AccessArticle

A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes

by Martina Palomino-Schätzlein, Rubén Lamas-Domingo, Andreea Ciudin, Patricia Gutiérrez-Carcedo, Rosó Marés, Carolina Aparicio-Gómez, Cristina Hernández, Rafael Simó and José Raúl Herance

J. Clin. Med. 2020, 9(6), 1619; https://doi.org/10.3390/jcm9061619 - 27 May 2020

Cited by 20 | Viewed by 3667

Abstract

Clinical parameters used in type 2 diabetes mellitus (T2D) diagnosis and monitoring such as glycosylated haemoglobin (HbA1c) are often unable to capture important information related to diabetic control and chronic complications. In order to search for additional biomarkers, we performed a pilot study [...] Read more.

Clinical parameters used in type 2 diabetes mellitus (T2D) diagnosis and monitoring such as glycosylated haemoglobin (HbA1c) are often unable to capture important information related to diabetic control and chronic complications. In order to search for additional biomarkers, we performed a pilot study comparing T2D patients with healthy controls matched by age, gender, and weight. By using ¹H-nuclear magnetic resonance (NMR) based metabolomics profiling of red blood cells (RBCs), we found that the metabolic signature of RBCs in T2D subjects differed significantly from non-diabetic controls. Affected metabolites included glutathione, 2,3-bisphophoglycerate, inosinic acid, lactate, 6-phosphogluconate, creatine and adenosine triphosphate (ATP) and several amino acids such as leucine, glycine, alanine, lysine, aspartate, phenylalanine and tyrosine. These results were validated by an independent cohort of T2D and control patients. An analysis of the pathways in which these metabolites were involved showed that energetic and redox metabolism in RBCs were altered in T2D, as well as metabolites transported by RBCs. Taken together, our results revealed that the metabolic profile of RBCs can discriminate healthy controls from T2D patients. Further research is needed to determine whether metabolic fingerprint in RBC could be useful to complement the information obtained from HbA1c and glycemic variability as well as its potential role in the diabetes management. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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15 pages, 672 KiB

Open AccessArticle

Contemporary Cardiovascular Risk Assessment for Type 2 Diabetes Including Heart Failure as an Outcome: The Fremantle Diabetes Study Phase II

by Wendy A. Davis, Valentina Hellbusch, Michael L. Hunter, David G. Bruce and Timothy M. E. Davis

J. Clin. Med. 2020, 9(5), 1428; https://doi.org/10.3390/jcm9051428 - 11 May 2020

Cited by 7 | Viewed by 2774

Abstract

Background: Type 2 diabetes (T2D) cardiovascular disease (CVD) risk assessment has limitations. The aim of this study was to develop a risk equation adding heart failure (HF) to conventional major adverse cardiovascular events (MACE, myocardial infarction, stroke, and CVD death) and allowing for [...] Read more.

Background: Type 2 diabetes (T2D) cardiovascular disease (CVD) risk assessment has limitations. The aim of this study was to develop a risk equation adding heart failure (HF) to conventional major adverse cardiovascular events (MACE, myocardial infarction, stroke, and CVD death) and allowing for non-CVD death. Methods: 1551 community-based people with T2D (mean age 66 years, 52% males) were followed from baseline in 2008–2011 for five years to the first CVD event/death. Cox and competing risk regression identified predictors of three-point MACE and four-point MACE (including HF). Discrimination was assessed by the area under the receiver-operating characteristic curve (AUC) and calibration by the Hosmer-Lemeshow test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for a 10% five-year CVD risk cut-off. Results: 143 participants (9.2%) experienced a three-point MACE during 7,111 person-years of follow-up and 245 (15.8%) a four-point MACE during 6,896 person-years. The best model was the competing risk four-point MACE (221 predicted events (14.3%), AUC 0.82 (95% CI: 0.79–0.85), Hosmer-Lemeshow test, p = 0.17, sensitivity 79.2%, specificity 68.1%, PPV 31.8%, NPV 94.6%) with validation in 177 adults with T2D from an independent population (AUC 0.81 (0.74–0.89). Conclusions: A validated four-point MACE competing risk model reliably predicts key T2D CVD outcomes. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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13 pages, 2011 KiB

Open AccessArticle

Significance of Soluble CD93 in Type 2 Diabetes as a Biomarker for Diabetic Nephropathy: Integrated Results from Human and Rodent Studies

by Minyoung Lee, Ho Seon Park, Min Yeong Choi, Hak Zoo Kim, Sung Jin Moon, Ji Yoon Ha, ARim Choi, Young Woo Park, Jong Suk Park, Eui-Cheol Shin, Chul Woo Ahn and Shinae Kang

J. Clin. Med. 2020, 9(5), 1394; https://doi.org/10.3390/jcm9051394 - 8 May 2020

Cited by 11 | Viewed by 3067

Abstract

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would [...] Read more.

Cluster of differentiation 93 (CD93) is a glycoprotein expressed in activated endothelial cells. The extracellular portion of CD93 can be secreted as a soluble form (sCD93) under inflammatory conditions. As diabetic nephropathy (DN) is a well-known inflammatory disease, we hypothesized that sCD93 would be a new biomarker for DN. We prospectively enrolled 97 patients with type 2 diabetes and evaluated the association between serum sCD93 and DN prevalence. The association between CD93 and development of DN was investigated using human umbilical cord endothelial cells (HUVECs) in vitro and diabetic db/db mice in vivo. Subjects with higher sCD93 levels had a lower estimated glomerular filtration rate (eGFR). The sCD93 level was an independent determinant of both the albumin-to-creatinine ratio (ACR) and the eGFR. The risk of prevalent DN was higher in the high sCD93 group (adjusted odds ratio 7.212, 95% confidence interval 1.244–41.796, p = 0.028). In vitro, CD93 was highly expressed in HUVECs and both CD93 expression and secretion were upregulated after lipopolysaccharides (LPS) stimulation. In vivo, peritoneal and urine sCD93 levels and the renal glomerular expression of CD93 were significantly higher in the db/db mice than in the control db/m+ mice. These results suggest the potential of sCD93 as a candidate biomarker associated with DN. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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12 pages, 976 KiB

Open AccessArticle

Effect of Subcutaneous Insulin on Spirometric Maneuvers in Patients with Type 1 Diabetes: A Case-Control Study

by Enric Sánchez, Chadia Mizab, Ariadna Sauret, Ferran Barbé, Raquel Martí, Carolina López-Cano, Marta Hernández, Liliana Gutiérrez-Carrasquilla, Paola Carmona, Jessica González, Mireia Dalmases, Cristina Hernández, Rafael Simó and Albert Lecube

J. Clin. Med. 2020, 9(5), 1249; https://doi.org/10.3390/jcm9051249 - 25 Apr 2020

Cited by 3 | Viewed by 2556

Abstract

In order to compare spirometric maneuvers in adults according to the presence of type 1 diabetes, a case-control study including 75 patients with type 1 diabetes and 75 controls matched by sex, age, and body mass index were designed. In addition, 75 patients [...] Read more.

In order to compare spirometric maneuvers in adults according to the presence of type 1 diabetes, a case-control study including 75 patients with type 1 diabetes and 75 controls matched by sex, age, and body mass index were designed. In addition, 75 patients with type 1 diabetes were added to examine the potential the impact of subcutaneous insulin therapy on pulmonary function. Lung function measurements were assessed according to the global initiative for chronic obstructive lung disease guidelines. Basal insulin included long-acting insulin analogues and the delivered background insulin in patients with pump therapy. Bolus insulin included rapid-acting insulin analogues and the delivered insulin to cover postprandial hyperglycemias. Patients with type 1 diabetes showed lower spirometric values in comparison to the control group, together with a higher prevalence of forced expiratory volume in the first second (FEV1) <80% (10.7% vs. 2.7%, p = 0.044) and restrictive ventilatory pattern (10.7% vs. 0%, p = 0.006) The dose of basal insulin (U/kg/day) showed a negative correlation with forced vital capacity (FVC) (r = −0.205, p = 0.012) and FEV1 (r = −0.182, p = 0.026). The optimal cut-off value for identifying patients with a restrictive spirometric pattern was 0.5 U/kg/day of basal insulin. Additionally, basal insulin (U/kg/day) independently predicted the presence of both a restrictive spirometric pattern (OR = 77.1 (3.2 to 1816.6), p = 0.007) and an abnormal FEV1 (OR = 29.9 (1.5 to 562.8), p = 0.023). In patients with type 1 diabetes, higher basal insulin dosage seems to be related with an impairment of pulmonary function. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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10 pages, 657 KiB

Open AccessArticle

The Usefulness of Serum Biomarkers in the Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

by Cristina Hernández, Massimo Porta, Francesco Bandello, Jakob Grauslund, Simon P. Harding, Stephen J. Aldington, Catherine Egan, Ulrik Frydkjaer-Olsen, José García-Arumí, Jonathan Gibson, Gabriele E. Lang, Rosangela Lattanzio, Pascale Massin, Edoardo Midena, Berta Ponsati, Luísa Ribeiro, Peter Scanlon, José Cunha-Vaz and Rafael Simó

J. Clin. Med. 2020, 9(4), 1233; https://doi.org/10.3390/jcm9041233 - 24 Apr 2020

Cited by 12 | Viewed by 3339

Abstract

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric [...] Read more.

The main aim of this study was to evaluate the ability of serum biomarkers to predict the worsening of retinal neurodysfunction in subjects with type 2 diabetes. For this purpose, we measured selected molecules (N-epsilon-carboxy methyl lysine (CML), laminin P1 (Lam-P1), and asymmetric dimethylarginine (ADMA)) in the serum of 341 participants of the EUROCONDOR study at baseline, 24, and 48 weeks. Retinal neurodysfunction was assessed by measuring implicit time (IT) using multifocal electroretinography, and structural changes were examined by spectral domain–optical coherence tomography. The values of IT at baseline were directly correlated with baseline serum concentrations of CML (r = 0.135, p = 0.013). Furthermore, in the placebo group, increase in CML concentration throughout follow-up correlated with the IT (r = 0.20; p = 0.03). Baseline serum levels of CML also correlated with macular retinal thickness (RT) (r = 0.231; p < 0.001). Baseline Lam-P1 levels correlated with the increase of the RT at the end of follow-up in the placebo group (r = 0.22; p = 0.016). We provide evidence that CML may be a biomarker of both retinal neurodysfunction and RT, whereas Lam-P1 was associated with RT only. Therefore, circulating levels of these molecules could provide a complementary tool for monitoring the early changes of diabetic retinopathy (DR). Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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14 pages, 457 KiB

Open AccessArticle

Screening for Liver Fibrosis and Steatosis in a Large Cohort of Patients with Type 2 Diabetes Using Vibration Controlled Transient Elastography and Controlled Attenuation Parameter in a Single-Center Real-Life Experience

by Ioan Sporea, Ruxandra Mare, Alina Popescu, Silviu Nistorescu, Victor Baldea, Roxana Sirli, Adina Braha, Alexandra Sima, Romulus Timar and Raluca Lupusoru

J. Clin. Med. 2020, 9(4), 1032; https://doi.org/10.3390/jcm9041032 - 6 Apr 2020

Cited by 37 | Viewed by 3911

Abstract

Background: Type 2 diabetes mellitus (T2DM), obesity, hyperlipidemia, and hypertension are considered risk factors for developing non-alcoholic fatty liver disease (NAFLD). This study aims to assess steatosis and fibrosis severity in a cohort of T2DM patients, using vibration controlled transient elastography (VCTE) and [...] Read more.

Background: Type 2 diabetes mellitus (T2DM), obesity, hyperlipidemia, and hypertension are considered risk factors for developing non-alcoholic fatty liver disease (NAFLD). This study aims to assess steatosis and fibrosis severity in a cohort of T2DM patients, using vibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP). Material and method: We performed a prospective study in which, in each patient, we aimed for 10 valid CAP and liver stiffness measurements (LSM). To discriminate between fibrosis stages, we used the following VCTE cut-offs: F ≥ 2–8.2 kPa, F ≥ 3–9.7 kPa, and F4 - 13.6 kPa. To discriminate between steatosis stages, we used the following CAP cut-offs: S1 (mild) – 274 dB/m, S2 (moderate) – 290dB/m, S3 (severe) – 302dB/m. Results: During the study period, we screened 776 patients; 60.3% had severe steatosis, while 19.4% had advanced fibrosis. Female gender, BMI, waist circumference, elevated levels of AST, total cholesterol, triglycerides, blood glucose, and high LSM were associated with severe steatosis (all p-value < 0.05). BMI, waist circumference, elevated levels of AST, HbA1c, and CAP were associated with advanced fibrosis (all p-values < 0.05). Conclusion: Higher BMI (obesity) comprises a higher risk of developing severe steatosis and fibrosis. Individualized screening strategies should be established for NAFLD according to different BMI. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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12 pages, 683 KiB

Open AccessArticle

Effect of Glucose Improvement on Nocturnal Sleep Breathing Parameters in Patients with Type 2 Diabetes: The Candy Dreams Study

by Liliana Gutiérrez-Carrasquilla, Carolina López-Cano, Enric Sánchez, Ferran Barbé, Mireia Dalmases, Marta Hernández, Angela Campos, Anna Michaela Gaeta, Paola Carmona, Cristina Hernández, Rafael Simó and Albert Lecube

J. Clin. Med. 2020, 9(4), 1022; https://doi.org/10.3390/jcm9041022 - 4 Apr 2020

Cited by 7 | Viewed by 2945

Abstract

Type 2 diabetes exerts a negative impact on sleep breathing. It is unknown whether a long-term improvement in glycemic control ameliorates this effect. We conducted an interventional study with 35 patients with type 2 diabetes and obstructive sleep apnea (OSA) to explore this. [...] Read more.

Type 2 diabetes exerts a negative impact on sleep breathing. It is unknown whether a long-term improvement in glycemic control ameliorates this effect. We conducted an interventional study with 35 patients with type 2 diabetes and obstructive sleep apnea (OSA) to explore this. At home, sleep breathing parameters were assessed at baseline and after a 4-month period in which antidiabetic therapy was intensified. Patients who decreased their body mass index ≥2kg/m² were excluded. Those with an HbA1c reduction ≥0.5% were considered good responders (n = 24). After the follow-up, good responders exhibited an improvement in the apnea–hypopnea index (AHI: 26-1 (95% IC: 8.6–95.0) vs. 20.0 (4.0–62.4) events/hour, p = 0.002) and in time with oxygen saturation below 90% (CT90: 13.3 (0.4–69.0) vs. 8.1 (0.4–71.2) %, p = 0.002). No changes were observed in the group of non–responders (p = 0.722 and p = 0.138, respectively). The percentage of moderate and severe OSA decreased among good responders (p = 0.040). In the wider population, the change in HbA1c correlated positively to decreases in AHI (r = 0.358, p = 0.035) and negatively to increases in the minimum arterial oxygen saturation (r = −0.386, p = 0.039). Stepwise multivariate regression analysis showed that baseline AHI and the absolute change in HbA1c independently predicted decreased AHI (R² = 0.496). The improvement of glycemic control exerts beneficial effects on sleep breathing parameters in type 2 diabetes, which cannot be attributed merely to weight loss. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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14 pages, 1228 KiB

Open AccessArticle

Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial

by Eugene Han, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang and Bong-Soo Cha

J. Clin. Med. 2020, 9(1), 259; https://doi.org/10.3390/jcm9010259 - 18 Jan 2020

Cited by 54 | Viewed by 4802

Abstract

Despite the benefits of pioglitazone in the treatment of non-alcoholic fatty liver disease (NAFLD), many treated patients continue to experience disease progression. We aimed to investigate the additive effect of ipragliflozin on NAFLD in patients with type 2 diabetes treated with metformin and [...] Read more.

Despite the benefits of pioglitazone in the treatment of non-alcoholic fatty liver disease (NAFLD), many treated patients continue to experience disease progression. We aimed to investigate the additive effect of ipragliflozin on NAFLD in patients with type 2 diabetes treated with metformin and pioglitazone. In this 24-week randomized controlled trial, 44 patients with type 2 diabetes and comorbid NAFLD were either randomized to receive 50 mg/day of ipragliflozin as an add-on treatment (n = 29) or maintained on metformin and pioglitazone (n = 15). The fatty burden was assessed using the fatty liver index, NAFLD liver fat score, and controlled attenuation parameter (CAP). Changes in fat and muscle depots were measured by dual-energy x-ray absorptiometry and abdominal computed tomography scans. The enrolled patients were relatively controlled (mean baseline glycated hemoglobin of 6.6% ± 0.6%) and centrally obese (mean waist circumference of 101.6 ± 10.9 cm). At week 24, patients in the ipragliflozin add-on group exhibited reduced hepatic fat content (fatty liver index: −9.8 ± 1.9, p = 0.002; NAFLD liver fat score: −0.5 ± 0.2, p = 0.049; CAP: −8.2 ± 7.8 dB/m², p = 0.133). Ipragliflozin add-on therapy also reduced whole-body visceral fat and the ratio of visceral to subcutaneous fat (change in whole-body visceral fat: −69.6 ± 21.5 g; change in abdominal visceral fat: −26.2 ± 3.7 cm²; abdominal visceral to subcutaneous fat ratio: −0.15 ± 0.04; all p < 0.05). In conclusion, ipragliflozin treatment significantly ameliorates liver steatosis and reduces excessive fat in euglycemic patients with type 2 diabetes and NAFLD taking metformin and pioglitazone. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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Review

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23 pages, 1540 KiB

Open AccessReview

Analysis of Effectiveness and Psychological Techniques Implemented in mHealth Solutions for Middle-Aged and Elderly Adults with Type 2 Diabetes: A Narrative Review of the Literature

by Julia Vázquez-de Sebastián, Andreea Ciudin and Carmina Castellano-Tejedor

J. Clin. Med. 2021, 10(12), 2701; https://doi.org/10.3390/jcm10122701 - 18 Jun 2021

Cited by 10 | Viewed by 5183

Abstract

Background: in diabetes, multiple mHealth solutions were produced and implemented for self-management behaviors. However, little research on the effectiveness of psychological techniques implemented within these mHealth solutions was carried out, and even less with the elderly population where technological barriers might exist. Reliable [...] Read more.

Background: in diabetes, multiple mHealth solutions were produced and implemented for self-management behaviors. However, little research on the effectiveness of psychological techniques implemented within these mHealth solutions was carried out, and even less with the elderly population where technological barriers might exist. Reliable evidence generated through a comprehensive evaluation of mHealth interventions may accelerate its growth for successful long-term implementation and to help to experience mHealth benefits in an enhanced way in all ages. Objective: this study aimed to review mHealth solutions for diabetes self-management in older adults (adherence to treatments and glycemic control) by analyzing the effectiveness of specific psychological techniques implemented. Methods: a narrative review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed (Medline) and American Psychological Association (APA) PsycInfo databases were searched for published papers that addressed eHealth solutions’ effectiveness for diabetes self-management. Studies in English, Spanish, and/or German of any design were screened, with no time constraints regarding the year of publication. A qualitative analysis of the selected papers was conducted in several steps. Results: this review found 38 studies setting up and analyzing mHealth solutions for older adults. Most research showed improvements in HbA1c, self-management behaviors, and medication adherence in T2DM patients post intervention. However, different mid-to-long term effects were found across studies, specifically concerning the maintenance and adherence to healthy behaviors. The most employed psychological framework was CBT, including techniques such as self-monitoring of outcome behaviors (mostly targeting glycemia measurements and healthy habits as physical activity and/or diet), tailored motivational feedback from medical staff, and psychoeducation or health coaches. The most successful mHealth intervention combined the feature of tailored feedback messages, interactive communication with healthcare professionals, and multifaceted functions. Conclusions: there is a lack of elaborate and detailed information in the literature regarding the factors considered in the design and development of mHealth solutions used as interventions for T2DM self-management in the elderly. Documentation and inclusion of such vital information will foster a transparent and shared decision-making process that will ultimately lead to the development of useful and user-friendly self-management apps that can enhance the quality of life for diabetes patients. Further research adapting mHealth solutions to older adults’ sensory deficits is necessary. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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46 pages, 650 KiB

Open AccessReview

Altered Metabolome of Lipids and Amino Acids Species: A Source of Early Signature Biomarkers of T2DM

by Ahsan Hameed, Patrycja Mojsak, Angelika Buczynska, Hafiz Ansar Rasul Suleria, Adam Kretowski and Michal Ciborowski

J. Clin. Med. 2020, 9(7), 2257; https://doi.org/10.3390/jcm9072257 - 16 Jul 2020

Cited by 33 | Viewed by 7118

Abstract

Diabetes mellitus, a disease of modern civilization, is considered the major mainstay of mortalities around the globe. A great number of biochemical changes have been proposed to occur at metabolic levels between perturbed glucose, amino acid, and lipid metabolism to finally diagnoe diabetes [...] Read more.

Diabetes mellitus, a disease of modern civilization, is considered the major mainstay of mortalities around the globe. A great number of biochemical changes have been proposed to occur at metabolic levels between perturbed glucose, amino acid, and lipid metabolism to finally diagnoe diabetes mellitus. This window period, which varies from person to person, provides us with a unique opportunity for early detection, delaying, deferral and even prevention of diabetes. The early detection of hyperglycemia and dyslipidemia is based upon the detection and identification of biomarkers originating from perturbed glucose, amino acid, and lipid metabolism. The emerging “OMICS” technologies, such as metabolomics coupled with statistical and bioinformatics tools, proved to be quite useful to study changes in physiological and biochemical processes at the metabolic level prior to an eventual diagnosis of DM. Approximately 300–400 such metabolites have been reported in the literature and are considered as predicting or risk factor-reporting metabolic biomarkers for this metabolic disorder. Most of these metabolites belong to major classes of lipids, amino acids and glucose. Therefore, this review represents a snapshot of these perturbed plasma/serum/urinary metabolic biomarkers showing a significant correlation with the future onset of diabetes and providing a foundation for novel early diagnosis and monitoring the progress of metabolic syndrome at early symptomatic stages. As most metabolites also find their origin from gut microflora, metabolism and composition of gut microflora also vary between healthy and diabetic persons, so we also summarize the early changes in the gut microbiome which can be used for the early diagnosis of diabetes. Full article

(This article belongs to the Special Issue Pathophysiology and Complications of Type 2 Diabetes Mellitus)

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