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Special Issue "Type 2 Diabetes: Update on Pathophysiology and Treatment"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: 15 April 2019

Special Issue Editor

Guest Editor
Dr. Tomoaki Morioka

Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University, Osaka, Japan
Website | E-Mail
Interests: type 2 diabetes, obesity, leptin, adipokines, atherosclerosis, beta-cell function

Special Issue Information

Dear Colleagues,

Type 2 diabetes and its complications are among the most important health problems in the world. Nowadays, it is widely recognized that type 2 diabetes is associated not only with cardiovascular mortality, but also with poor quality of life due, for example, to chronic kidney disease, sarcopenia, cancer, and dementia. To overcome these problems, it is important to better understand the disease process of type 2 diabetes and its complications with the goal of developing new treatment strategies.

This Special Issue of the Journal of Clinical Medicine aims to invite authors to contribute original research articles as well as review articles related to the pathophysiology and treatment of type 2 diabetes and its vascular and non-vascular complications.

Dr. Tomoaki Morioka
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • type 2 diabetes
  • insulin secretion
  • insulin resistance
  • glucagon
  • hypoglycemia
  • obesity
  • adipocytokines
  • atherosclerosis
  • cardiovascular diseases
  • diabetic kidney disease
  • cancer
  • sarcopenia
  • dementia
  • exercise
  • antidiabetic drugs
  • incretin hormones

Published Papers (8 papers)

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Research

Open AccessArticle Factors Influencing Variations in Hospitalization for Diabetes with Hypoglycemia
J. Clin. Med. 2018, 7(10), 367; https://doi.org/10.3390/jcm7100367
Received: 10 September 2018 / Revised: 8 October 2018 / Accepted: 12 October 2018 / Published: 18 October 2018
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Abstract
Many studies have explored risk factors associated with Hypoglycemia (HG) and examined the variation in healthcare utilization among HG patients. However, most of these studies failed to integrate a comprehensive list of personal risk factors in their investigations. This empirical study employed the
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Many studies have explored risk factors associated with Hypoglycemia (HG) and examined the variation in healthcare utilization among HG patients. However, most of these studies failed to integrate a comprehensive list of personal risk factors in their investigations. This empirical study employed the Behavioral Model (BM) of health care utilization as a framework to investigate diabetes’ hospitalizations with HG. The national inpatient sample with all non-pregnant adult patients admitted to hospitals’ emergency departments and diagnosed with HG from 2012 to 2014 was used. Personal factors were grouped as predictors of the length of stay and the total charges incurred for hospitalization. High-risk profiles of hospitalized HG patients were identified. The analysis shows the need for care factors are the most influential predictors for lengthy hospitalization. The predisposing factors have a limited influence, while enabling factors influence the variation in hospital total charges. The presence of renal disease and diabetes mellitus (DM) complications played a key role in predicting hospital utilization. Furthermore, age, socio-economic status (SES), and the geographical location of the patients were also found to be vital factors in determining the variability in utilization among HG patients. Findings provide practical applications for targeting the high-risk HG patients for interventions. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Inhibitory Effects of Intranasal Administration of Insulin on Fat Oxidation during Exercise Are Diminished in Young Overweight Individuals
J. Clin. Med. 2018, 7(10), 308; https://doi.org/10.3390/jcm7100308
Received: 29 August 2018 / Revised: 25 September 2018 / Accepted: 26 September 2018 / Published: 28 September 2018
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Abstract
It remains unknown whether the high insulin (INS) levels in the brain affect fat oxidation during exercise. We examined the effects of the intranasal administration of INS, which increases the INS concentration in the cerebrospinal fluid when peripheral effects are lacking, on the
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It remains unknown whether the high insulin (INS) levels in the brain affect fat oxidation during exercise. We examined the effects of the intranasal administration of INS, which increases the INS concentration in the cerebrospinal fluid when peripheral effects are lacking, on the maximum fat oxidation rate (maxFOR) and its intensity (FATmax) during exercise in 15 young normal-weight (N group) and eight young overweight (O group) individuals. On two separate days, either INS or placebo (PL) was randomly administered intranasally before a graded exercise test. Indirect calorimetry was used to assess maxFOR and FATmax during exercise. Blood INS and glucose levels did not change after INS administration. In the N group, maxFOR and FATmax were significantly smaller in the INS trial than in the PL trial. MaxFOR was significantly smaller in the O group than in the N group and was not influenced by INS administration. Exercise-induced elevation in blood epinephrine levels tended to be reduced by INS administration only in the N group. Intranasal INS administration reduces fat oxidation during exercise without any peripheral effects, possibly by suppressing sympathetic nerve activity. This inhibitory effect is diminished in overweight subjects, suggesting that cerebral insulin effects are attenuated in this population. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Pioglitazone Reduces Dementia Risk in Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Analysis
J. Clin. Med. 2018, 7(10), 306; https://doi.org/10.3390/jcm7100306
Received: 10 September 2018 / Revised: 20 September 2018 / Accepted: 23 September 2018 / Published: 27 September 2018
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Abstract
Background: The beneficial effect of pioglitazone on dementia requires confirmation. Methods: The database of Taiwan’s National Health Insurance was used to enroll a propensity score-matched-pair cohort of patients who had ever used pioglitazone and patients who had never used pioglitazone from Taiwanese patients
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Background: The beneficial effect of pioglitazone on dementia requires confirmation. Methods: The database of Taiwan’s National Health Insurance was used to enroll a propensity score-matched-pair cohort of patients who had ever used pioglitazone and patients who had never used pioglitazone from Taiwanese patients with newly diagnosed diabetes mellitus during 1999–2008. The patients were to be alive on 1 January 2009 and were followed up for dementia until 31 December 2011. Hazard ratios were estimated using the Cox proportional hazards model. Results: There were 11,011 never users and 11,011 ever users of pioglitazone, with respective numbers of incident dementia of 123 and 91. The overall hazard ratio was 0.716 (95% confidence interval: 0.545–0.940) for ever users versus never users. The hazard ratios for the first (<11.0 months), second (11.0–19.6 months) and third (>19.6 months) tertiles of cumulative duration were 0.806 (0.544–1.193), 0.654 (0.430–0.994) and 0.694 (0.469–1.026), respectively. When cumulative duration was treated as a continuous variable, the hazard ratio was 0.987 (0.976–0.998). In subgroup analyses, the beneficial effect was mainly observed in patients who had not been treated with metformin. Among metformin ever users, the hazard ratio for dementia for pioglitazone ever users versus never users was 0.802 (0.580–1.109); and was 0.494 (0.284–0.857) among never users of metformin. No interaction between pioglitazone and major risk factors of dementia (i.e., stroke, hypoglycemia, head injury and Parkinson’s disease) was observed. Conclusions: Pioglitazone use is associated with a lower risk of dementia, especially when it is used in never users of metformin and has been used for more than 20 months. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Development of a Prediction Model for Colorectal Cancer among Patients with Type 2 Diabetes Mellitus Using a Deep Neural Network
J. Clin. Med. 2018, 7(9), 277; https://doi.org/10.3390/jcm7090277
Received: 21 August 2018 / Revised: 8 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
Objectives: Observational studies suggested that patients with type 2 diabetes mellitus (T2DM) presented a higher risk of developing colorectal cancer (CRC). The current study aims to create a deep neural network (DNN) to predict the onset of CRC for patients with T2DM. Methods:
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Objectives: Observational studies suggested that patients with type 2 diabetes mellitus (T2DM) presented a higher risk of developing colorectal cancer (CRC). The current study aims to create a deep neural network (DNN) to predict the onset of CRC for patients with T2DM. Methods: We employed the national health insurance database of Taiwan to create predictive models for detecting an increased risk of subsequent CRC development in T2DM patients in Taiwan. We identified a total of 1,349,640 patients between 2000 and 2012 with newly diagnosed T2DM. All the available possible risk factors for CRC were also included in the analyses. The data were split into training and test sets with 97.5% of the patients in the training set and 2.5% of the patients in the test set. The deep neural network (DNN) model was optimized using Adam with Nesterov’s accelerated gradient descent. The recall, precision, F1 values, and the area under the receiver operating characteristic (ROC) curve were used to evaluate predictor performance. Results: The F1, precision, and recall values of the DNN model across all data were 0.931, 0.982, and 0.889, respectively. The area under the ROC curve of the DNN model across all data was 0.738, compared to the ideal value of 1. The metrics indicate that the DNN model appropriately predicted CRC. In contrast, a single variable predictor using adapted the Diabetes Complication Severity Index showed poorer performance compared to the DNN model. Conclusions: Our results indicated that the DNN model is an appropriate tool to predict CRC risk in patients with T2DM in Taiwan. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Short Course of Insulin Treatment versus Metformin in Newly Diagnosed Patients with Type 2 Diabetes
J. Clin. Med. 2018, 7(9), 235; https://doi.org/10.3390/jcm7090235
Received: 10 August 2018 / Revised: 20 August 2018 / Accepted: 21 August 2018 / Published: 23 August 2018
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Abstract
The ß-cell dysfunction of type 2 diabetes is partly reversible. The optimal time window to induce glycemic remission is uncertain; short courses of insulin treatment have been tested as a strategy to induce remission. In a pilot study in 38 newly-diagnosed patients, we
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The ß-cell dysfunction of type 2 diabetes is partly reversible. The optimal time window to induce glycemic remission is uncertain; short courses of insulin treatment have been tested as a strategy to induce remission. In a pilot study in 38 newly-diagnosed patients, we assessed the time-course of insulin sensitivity and ß-cell function (by repeat oral glucose tolerance tests) following a 6-week basal insulin treatment compared to metformin monotherapy in equipoised glycemic control. At 6 weeks, insulin secretion and sensitivity were increased in both groups whilst ß-cell glucose sensitivity was unchanged. From this time onwards, in the insulin group glycemia started to rise at 3 months, and was no longer different from baseline at 1 year. The initial improvement in insulin secretion and sensitivity dissipated. In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group. A short course of basal insulin in newly-diagnosed patients does not appear to offer clinical advantage over recommended initiation with metformin. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
Open AccessArticle Albuminuria Increases All-Cause Mortality in Japanese Patients with Type 2 Diabetes Mellitus
J. Clin. Med. 2018, 7(9), 234; https://doi.org/10.3390/jcm7090234
Received: 19 July 2018 / Revised: 14 August 2018 / Accepted: 21 August 2018 / Published: 23 August 2018
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Abstract
Previous studies have reported that diabetic kidney disease is associated with cardiovascular events and death. Little is known about the independent association of albuminuria and estimated glomerular filtration rate (eGFR), with mortality in Asian patients with type 2 diabetes mellitus (T2DM) without renal
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Previous studies have reported that diabetic kidney disease is associated with cardiovascular events and death. Little is known about the independent association of albuminuria and estimated glomerular filtration rate (eGFR), with mortality in Asian patients with type 2 diabetes mellitus (T2DM) without renal failure. We conducted a historical cohort study to clarify this issue in Japanese patients with T2DM. In this study, we recruited 385 patients with T2DM, who never had chronic renal failure (eGFR < 30 mL/min/1.73 m2 at baseline) and malignant diseases. With the end point of all-cause mortality, Cox regression analysis was performed. During the observational period of 7 years, 54 patients died. Cox regression analysis adjusted for confounding factors such as age, duration of diabetes, body mass index, and HbA1c, and showed that urinary albumin level was significantly associated with the mortality [hazard ratio (HR) = 1.32, 95% confidence interval (CI) = 1.03–1.70 per standard deviation (SD) increase, p = 0.031]. After additional adjustment for eGFR, the association remained significant (HR = 1.32, 95% CI = 1.02–1.70 per SD increase, p = 0.033). On the other hand, eGFR was not associated with the mortality. The present study showed that higher urinary albumin was associated with increased all-cause mortality in T2DM, independently of eGFR. These findings suggest that, regardless of eGFR, albuminuria is important for the increased risk of mortality in Japanese T2DM patients without chronic renal failure (eGFR < 30 mL/min/1.73 m2). However, because of several limitations, further large-scale longitudinal studies are necessary to confirm the present study. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
Open AccessArticle Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and Renal Function in Type 2 Diabetic Patients
J. Clin. Med. 2018, 7(8), 220; https://doi.org/10.3390/jcm7080220
Received: 17 July 2018 / Revised: 13 August 2018 / Accepted: 14 August 2018 / Published: 16 August 2018
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Abstract
The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D
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The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2 diabetes (T2D) is undetermined and controversial. This study aims to evaluate the impact of the main mtDNA haplogroups on glycaemic control and renal function in a Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical and metabolic parameters were assessed and mtDNA haplogroup was determined in each individual. Distribution of the different haplogroups was similar in diabetic and healthy populations and, as expected, T2D patients showed poorer glycaemic control and renal function than controls. T2D patients belonging to the JT haplogroup (polymorphism m.4216T>C) displayed statistically significant higher levels of fasting glucose and HbA1c than those of the other haplogroups, suggesting a poorer glycaemic control. Furthermore, diabetic patients with the JT haplogroup showed a worse kidney function than those with other haplogroups, evident by higher levels of serum creatinine, lower estimated glomerular filtration rate (eGFR), and slightly higher (although not statistically significant) urinary albumin-to-creatinine ratio. Our results suggest that JT haplogroup (in particular, change at position 4216 of the mtDNA) is associated with poorer glycaemic control in T2D, which can trigger the development of diabetic nephropathy. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Heat Shock Protein 70 Gene Single Nucleotide Polymorphism and Diabetic Foot Ulcer. Is There Any Relationship?
J. Clin. Med. 2018, 7(8), 187; https://doi.org/10.3390/jcm7080187
Received: 29 June 2018 / Revised: 24 July 2018 / Accepted: 24 July 2018 / Published: 27 July 2018
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Abstract
Objective: The study aims to investigate the potential role of C2437T (Met493Thr) single nucleotide polymorphism (SNP) of the heat shock protein (HSP) 70 in diabetic foot ulcer patients. Methods: In this prospective cohort study, SNP of the HSP70 hom gene, also called HSPA1L,
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Objective: The study aims to investigate the potential role of C2437T (Met493Thr) single nucleotide polymorphism (SNP) of the heat shock protein (HSP) 70 in diabetic foot ulcer patients. Methods: In this prospective cohort study, SNP of the HSP70 hom gene, also called HSPA1L, was studied among diabetic patients with an ulcer (Group A: n = 50), diabetic patients without an ulcer (Group B: n = 50), and healthy subjects (Group C: n = 50). Results: There was a higher frequency of T/T genotype in group A (76%) as compared to group B (44%) and group C (14%). Moreover, the frequency of T allele was 7.3% in group A, 5.5% in group B, and 3.9% in group C. C allele frequency was 2.6%, 4.4%, and 6.1% in group A, group B, and group C, respectively. In group A, the odds ratio and risk ratio were 19-fold and 5-fold, respectively, for the HSP70 hom T/T homozygous gene compared to B (OR 19.45; RR 5.42; X2 38.8, p < 0.0001). Moreover, 4-fold and 1.75-fold ratios have been compared with group C (OR 4.03; RR 1.72; X2 10.6, p < 0.001). No significant difference in genotype was observed in group B and group C. Conclusions: There is a significant and positive association of hspHSP70 hom polymorphism restricted to T allele in homozygous and heterozygous states among diabetic foot ulcer (DFU) patients. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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