Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis.

BACKGROUND: It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD). Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). METHODS: In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1-4) was used to determine visit-to-visit HbA1c variability. RESULTS: Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients). The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0-6.9%]_Q1 (P = 0.006), HVS [6.0-6.9%]_Q2 (P = 0.013), HVS [6.0-6.9%]_Q3 (P = 0.018), and HVS [7.0-7.9%]_Q3 (P = 0.040). CONCLUSION: To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

Three-dimensional Multistructural Quantitative Photoacoustic and US Imaging of Human Feet in Vivo.

Background Monitoring the microcirculation in human feet is crucial in assessing peripheral vascular diseases, such as diabetic foot. However, conventional imaging modalities are more focused on diagnosis in major arteries, and there are limited methods to provide microvascular information in early stages of the disease. Purpose To investigate a three-dimensional (3D) noncontrast bimodal photoacoustic (PA)/US imaging system that visualizes the human foot morphologically and also reliably quantifies podiatric vascular parameters noninvasively. Materials and Methods A clinically relevant PA/US imaging system was combined with a foot scanner to obtain 3D PA and US images of the human foot in vivo. Healthy participants were recruited from September 2020 to June 2021. The collected 3D PA and US images were postprocessed to present structural information about the foot. The quantitative reliability was evaluated in five repeated scans of 10 healthy feet by calculating the intraclass correlation coefficient and minimal detectable change, and the detectability of microvascular changes was tested by imaging 10 healthy feet intentionally occluded with use of a pressure cuff (160 mm Hg). Statistically significant difference is indicated with P values. Results Ten feet from six healthy male volunteers (mean age ± standard deviation, 27 years ± 3) were included. The foot images clearly visualized the structure of the vasculature, bones, and skin and provided such functional information as the total hemoglobin concentration (HbT), hemoglobin oxygen saturation (SO2), vessel density, and vessel depth. Functional information from five independent measurements of 10 healthy feet was moderately reliable (intraclass correlation coefficient, 0.51-0.74). Significant improvements in HbT (P = .006) and vessel density (P = .046) as well as the retention of SO2 were observed, which accurately described the microvascular change due to venous occlusion. Conclusion Three-dimensional photoacoustic and US imaging was able to visualize morphologic and physiologic features of the human foot, including the peripheral microvasculature, in healthy volunteers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mezrich in this issue.

WormBase: a modern Model Organism Information Resource.

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by leveraging commercial cloud offerings. We conclude with a description of WormBase's role as a founding member of the nascent Alliance of Genome Resources.

Long-Term Changes in HbA1c According to Blood Glucose Control Status During the First 3 Months After Visiting a Tertiary University Hospital.

BACKGROUND: We evaluated patients visiting a tertiary university hospital due to a diagnosis of diabetes with a goal of achieving blood glucose control and evaluated blood glucose persistence over 7 years according to the change in blood glucose evident at 3 months after the first visit. METHODS: Patients treated from 2009 to 2013 were categorized into four groups according to the change in HbA1c levels during the first 3 months of follow-up (Best_group, ≥ 1.6% decrease; Better_group, 0.5-1.5% decrease; Neutral_group, maintained at -0.4% to +0.4%; Worse_group, ≥ 0.5% increase). Each patient's blood glucose control status was then monitored for 7 years. The incidence of stroke and acute coronary syndrome during this period was confirmed. RESULTS: Overall, 9,776 patients were included. HbA1c values were lower in the Best_group than in the other groups at all time points (all P < 0.001). The rate of reaching targets of < 6.5% or < 7.0% HbA1c decreased over time; the rate at which the estimated glomerular filtration rate decreased to < 30 or < 60 mL/min/1.73m² increased over time (all trends, P < 0.01). CONCLUSION: Blood glucose control status in the first 3 months after initiating hospital care enabled estimation of the patient's glycemic control status for the next 7 years. In cases with poor initial blood glucose control, a new or more active method of blood glucose control should be sought.

Safety and effectiveness of linagliptin in Korean patients with type 2 diabetes: A postmarketing surveillance study.

We designed a postmarketing surveillance study of linagliptin for patients with type 2 diabetes (T2D) in Korea. This prospective, observational, multicentre study investigated the safety and glycaemic effectiveness of linagliptin as monotherapy or combination therapy with other antidiabetic drugs in routine clinical practice. Endpoints were the incidence of adverse drug reactions (ADRs) and the change in HbA1c. Overall, 3119 and 2171 patients were included in the safety and effectiveness analysis sets, respectively. A total of 56 patients (1.8%) experienced ADRs. The most common ADR was gastrointestinal disorders (0.7%), followed by metabolism and nutrition disorders (0.5%). ADRs of special interest, including pancreatic diseases, cardiac diseases and hypoglycaemia, occurred in 12 patients, 11 of whom had hypoglycaemia, while one had a skin lesion. Mean HbA1c change during the study period was -0.8%. Lower body mass index, shorter diabetes duration and higher baseline HbA1c were independently associated with a better effectiveness, while the presence of diabetic complications, dyslipidaemia and the use of sulphonylureas were associated with a poor response. In conclusion, linagliptin showed an excellent safety profile and glycaemic effectiveness in Korean patients with T2D.

Discontinuation rate and reason for discontinuation after sodium-glucose cotransporter 2 inhibitor prescription in real clinical practice.

WHAT IS KNOWN AND OBJECTIVES: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel antidiabetic agents that have advantages of weight loss and prevention of cardiovascular diseases. However, SGLT2i have various side effects. To understand their effectiveness, we analysed patients who had discontinued the use of dapagliflozin, an SGLT2i, 3 months after the initial prescription. We evaluated the discontinuation rate of dapagliflozin and the incidence rate of its side effects. METHODS: Patients who were initially prescribed dapagliflozin for blood sugar control from December 2014 to December 2016 were analysed. Data of patients in whom dapagliflozin administration was discontinued 90 days after initial prescription were collected separately, and the reasons were evaluated by a direct chart review. RESULTS AND DISCUSSION: A total of 8.96% (149/1663) patients discontinued dapagliflozin or switched medications within 3 months. Dapagliflozin was discontinued in 24.8% (37/149) of cases due to unexpected causes such as increased blood sugar and weight gain. The patients who discontinued dapagliflozin use due to side effects comprised 49.7% (74/149). Two major side effects were genital tract infection in women (P < .001 compared with men) and urinary tract infection, which increased with age (P = .030). Malpractice of medical personnel, insurance problems or causes of termination not related to dapagliflozin use comprised 14.1% (21/149). WHAT IS NEW AND CONCLUSION: The incidence of side effects with dapagliflozin was not as high as expected. Physicians should consider instructions prior to prescribing dapagliflozin so that its discontinuation would decrease considerably.

Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function.

In this article, Figure 2F was incorrect. The correct panel is shown below. The authors sincerely apologise for this error.

Effectiveness and safety of exenatide in Korean patients with type 2 diabetes inadequately controlled with oral hypoglycemic agents: an observational study in a real clinical practice.

BACKGROUND: Randomized clinical trials have shown the efficacy and safety of short-acting exenatide in patients with type 2 diabetes mellitus (T2DM). The aim of this observational study was to investigate the effectiveness and safety of exenatide twice a day in Korean patients with T2DM who are suboptimally controlled with oral hypoglycemic agents. METHODS: This study was a post hoc analysis of multi-center (71 centers), prospective, observational, single-arm, post-marketing study of short-acting exenatide 5 to 10 µg twice a day from March 2008 to March 2014 and analyzed those who finished the follow-up over 20 weeks of medication. Changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight values before and after exenatide treatment were analyzed. Adverse events and adverse drug reactions were estimated in patients who were treated with exenatide at least once and for whom follow-up for safety has been completed. RESULTS: After 20 weeks treatment with exenatide, mean HbA1c and body weight were significantly reduced from 8.4% to 7.7% and from 83.4 kg to 80.2 kg, respectively (both p < 0.001). Subjects with higher baseline glucose and HbA1c levels showed an independent association with a greater reduction in glucose level. In addition, short duration of diabetes less than 5 years was an independent predictor for the improvement in glucose level. The majority of study subjects showed a reduction in both body weight and glucose level (63.3%) after exenatide treatment. In terms of safety profile, exenatide treatment was generally well-tolerated and the incidence of severe adverse event was rare (0.8%). The gastrointestinal side effects were most common and hypoglycemia was reported in 1.7% of subjects. CONCLUSION: In real clinical practice, 20 weeks treatment with short-acting exenatide was well tolerated and showed a significant body weight and glucose reduction in Korean patients with T2D who are suboptimally controlled with oral hypoglycemic agents. TRIAL REGISTRATION: ClinicalTirals.gov , number NCT02090673 , registered 14 February 2008.

The differences in the incidence of diabetes mellitus and prediabetes according to the type of HMG-CoA reductase inhibitors prescribed in Korean patients.

BACKGROUND: Very few studies conducted in Korea have investigated the relationship between statins and the incidence of diabetes. Therefore, we analyzed the progression from normal blood glucose to prediabetes and then to diabetes mellitus (DM) according to the type, intensity, and dose of statin prescribed. METHODS: Data of patients who were first prescribed statins between 2009 and 2011 were extracted from electronic medical records. Patients with normal blood glucose or prediabetes were observed for 4 years after initiation of statin therapy. RESULTS: A total of 2890 patients were included in our study and analyzed on the basis of the first statin they were prescribed. The incidence rate of DM in patients with prediabetes was 1.72 times that of patients with normal glucose levels (odds ratio = 1.72, 95% confidence interval = 1.41-2.10, P < .001). Regarding progression from normal blood glucose to prediabetes, the incidence rate of prediabetes was significantly lower in patients prescribed pitavastatin (odds ratio = 0.62, 95% confidence interval = 0.40-0.96, P = .031) compared to that in patients prescribed atorvastatin. Regarding the progression from normal blood glucose or prediabetes to DM, there were no significant differences among all statins. CONCLUSIONS: Lower DM incidence in patients prescribed pitavastatin appears to be primarily because of the lower rate of progression from normal blood glucose to prediabetes. These findings indicate that avoiding statins because of DM risk is unjustified and that clinicians should prescribe statins from the appropriate potency group.

Randomized, Open-Label, Parallel Group Study to Evaluate the Effect of Internet-Based Glucose Management System on Subjects with Diabetes in China.

OBJECTIVE: Large amounts of time and effort are needed to implement an Internet-based glucose monitoring system (IBGMS) in the clinical setting. This study was designed using research experience that was developed while implementing an IBGMS in Korea, and the research platform was modified to evaluate the efficacy of an IBGMS in controlling blood sugar in the Chinese population. METHODS: A randomized, open-label, parallel group design was used to evaluate the efficacy of an IBGMS among Chinese subjects with type 2 diabetes. Over a 6-month period, 182 subjects were evaluated in the IBGMS (n = 92) or control (n = 90) groups. RESULTS: After 3 months, the control group's HbA1c levels were reduced from 8.0% ± 0.8% to 7.3% ± 1.2% (p < 0.001) and the IBGMS group experienced a reduction from 7.9% ± 0.8% to 6.9% ± 0.7% (p < 0.001); the IBGMS group's end value was significantly lower (p = 0.014). The intragroup changes in the control and IBGMS groups were significant at the 3-month (p = 0.002) and 6-month (p < 0.01) follow-ups. Over this period, the HbA1c levels in the control group increased slightly (7.3% ± 1.1% to 7.4% ± 1.3%, p = 0.605), and the HbA1c levels in the IBGMS group decreased slightly (6.9% ± 0.7% to 6.7% ± 0.7%, p = 0.081). CONCLUSIONS: The IBGMS was effective in improving blood sugar levels among patients with diabetes. Therefore, IBGMS experience can be effectively transferred between institutions and countries.

Exploring the relationship among user satisfaction, compliance, and clinical outcomes of telemedicine services for glucose control.

BACKGROUND: Although research has shown that telemedicine services for blood glucose control can be useful in managing diabetes, the relationships among user satisfaction, compliance, and clinical outcomes have not been well studied. A positive assessment of telemedicine services can improve user satisfaction, which can increase compliance and improve clinical outcomes. These relationships are validated with actual telemedicine projects for diabetes management. MATERIALS AND METHODS: The assessment of user satisfaction for telemedicine services is composed of the following six variables: usefulness, ease of use, compatibility, facilitating conditions, accessibility, and intimacy. The relationship between user satisfaction and compliance or hemoglobin A1c (HbA1c) improvement was analyzed. Data were collected from 81 type 2 diabetic patients who used telemedicine services. We used multiple regression analysis, logistic regression analysis, simple linear regression, and the Wilcoxon signed-rank test to analyze the data. RESULTS: The user assessments of the telemedicine services were very high, ranging from 5.8 to 6 points. Of the six variables, compatibility, ease of use, intimacy, and usefulness had a positive effect on overall satisfaction (p<0.05). Overall satisfaction and compliance were positively correlated with HbA1c improvement. In addition, income level was also an important variable for overall satisfaction. CONCLUSIONS: Our results indicate that patient assessments of telemedicine services are important factors for clinical outcome improvement. In addition, higher satisfaction and more frequent self-assessments can improve clinical outcomes.

Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function.

BACKGROUND/AIMS: Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. METHODS: This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. RESULTS: The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity. CONCLUSION: In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.

Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years' duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups' gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

WormBase 2024: status and transitioning to Alliance infrastructure.

WormBase has been the major repository and knowledgebase of information about the genome and genetics of Caenorhabditis elegans and other nematodes of experimental interest for over 2 decades. We have 3 goals: to keep current with the fast-paced C. elegans research, to provide better integration with other resources, and to be sustainable. Here, we discuss the current state of WormBase as well as progress and plans for moving core WormBase infrastructure to the Alliance of Genome Resources (the Alliance). As an Alliance member, WormBase will continue to interact with the C. elegans community, develop new features as needed, and curate key information from the literature and large-scale projects.

Weight loss and side-effects of liraglutide and lixisenatide in obesity and type 2 diabetes mellitus.

AIMS: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) is used to treat obesity or type 2 diabetes mellitus (DM). We compared weight loss and side-effects between patients with and without DM using GLP-1 RA. METHODS: This was a retrospective cohort study based on electronic medical records. Patients were categorized into three groups: liraglutide without DM (LiRa_NL), liraglutide with DM (LiRa_DM), and lixisenatide with DM (LiXi_DM). Six-month outcomes were evaluated for weight loss, side-effect types, and onset discontinuation of GLP-1 RA. RESULTS: We enrolled 356 (190 LiRa_NL, 95 LiRa_DM, and 71 LiXi_DM) patients (women, 72.5 %; mean age, 43.7 ± 12.7 years; mean body mass index, 30.7 ± 5.2 kg/m2). The mean glycated hemoglobin (HbA1c) participants were 7.7 ± 2.1 %. Average weight loss was 2.9 ± 0.3 kg. The change in HbA1c was lower in the LiXi_DM group than in the LiRa_DM group (- 1.1 ± 0.2 % vs. - 0.4 ± 0.1 %, P < 0.05). The LiRa_DM group showed a more effective weight loss (- 3.0 ± 0.4 kg) than the LiXi_DM group (- 0.9 ± 0.4 kg) (P < 0.05). Approximately 30 % of the patients reported experiencing side-effects, with gastrointestinal side-effects being the most frequent (20.5 %). The median side-effect onset was 1.9 ± 0.1 months from first treatment. The rate of GLP-1 RA discontinuation was 72.8 %. Discontinuation rates due to side-effects were 75.7 %, 68.9 %, and 64.4 % in the LiRa_NL, LiRa_DM, and LiXi_DM groups, respectively. CONCLUSIONS: The LiRa_NL group showed the most weight loss, although the discontinuation rate was high. Most side-effects occurred at 1-2 months. When prescribing GLP-1 RA, education concerning side-effects and discontinuation is needed to enhance treatment adherence.

Glucometabolic control of once-weekly dulaglutide switched from DPP4 inhibitor versus daily empagliflozin add-on in patients with type 2 diabetes inadequately controlled with metformin, sulfonylurea, and DPP4 inhibitor: A randomised trial.

AIMS: To compare the effectiveness and safety of empagliflozin and dulaglutide in patients with type 2 diabetes (T2D) inadequately controlled by oral triple therapy. METHODS: In this 24-week, multi-center, randomized trial, patients with T2D and HbA1c level ≥7.5% (58 mmol/mol) on metformin, sulfonylurea, and dipeptidyl peptidase 4 inhibitor (DPP4-i) were randomly assigned into two groups: daily empagliflozin add-on or once-weekly dulaglutide switched from DPP4-i. The primary endpoint was changes from baseline HbA1c at 24 weeks. RESULTS: In total, 152 patients were recruited to the empagliflozin-added quadruple group (n = 76) or the switched-to-dulaglutide triple group (n = 76). At week 24, both groups showed significant reduction in HbA1c level from baseline with greater reduction with empagliflozin (the mean treatment difference: -0.27% [95% CI -0.50 to -0.04, p = 0.024]) (-2.88 mmol/mol [95% CI -5.37 to -0.39], p = 0.024). Empagliflozin significantly reduced body weight from baseline to week 24 (-1.72 kg [95% CI -1.98 to -0.59, p < 0.001]). No serious adverse events were reported with either empagliflozin or dulaglutide. CONCLUSIONS: Empagliflozin, compared with once-weekly dulaglutide switched from DPP4-i, demonstrated greater HbA1c reduction and weight loss in patients with T2D inadequately controlled with metformin, sulfonylurea, and DPP4-i. TRIAL REGISTRATION: cris.nih.go.kr (KCT0006157).

Predicting the Risk of Insulin-Requiring Gestational Diabetes before Pregnancy: A Model Generated from a Nationwide Population-Based Cohort Study in Korea.

BACKGRUOUND: The severity of gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. We aimed to generate a risk model for predicting insulin-requiring GDM before pregnancy in Korean women. METHODS: A total of 417,210 women who received a health examination within 52 weeks before pregnancy and delivered between 2011 and 2015 were recruited from the Korean National Health Insurance database. The risk prediction model was created using a sample of 70% of the participants, while the remaining 30% were used for internal validation. Risk scores were assigned based on the hazard ratios for each risk factor in the multivariable Cox proportional hazards regression model. Six risk variables were selected, and a risk nomogram was created to estimate the risk of insulin-requiring GDM. RESULTS: A total of 2,891 (0.69%) women developed insulin-requiring GDM. Age, body mass index (BMI), current smoking, fasting blood glucose (FBG), total cholesterol, and γ-glutamyl transferase were significant risk factors for insulin-requiring GDM and were incorporated into the risk model. Among the variables, old age, high BMI, and high FBG level were the main contributors to an increased risk of insulin-requiring GDM. The concordance index of the risk model for predicting insulin-requiring GDM was 0.783 (95% confidence interval, 0.766 to 0.799). The validation cohort's incidence rates for insulin-requiring GDM were consistent with the risk model's predictions. CONCLUSION: A novel risk engine was generated to predict insulin-requiring GDM among Korean women. This model may provide helpful information for identifying high-risk women and enhancing prepregnancy care.

Neutralizing interleukin-1beta (IL-1beta) induces beta-cell survival by maintaining PDX1 protein nuclear localization.

The transcription factor PDX1 plays a critical role during ß-cell development and in glucose-induced insulin gene transcription in adult ß-cells. Acute glucose exposure leads to translocalization of PDX1 to the nucleoplasm, whereas under conditions of oxidative stress, PDX1 shuttles from the nucleus to the cytosol. Here we show that cytosolic PDX1 expression correlated with ß-cell failure in diabetes. In isolated islets from patients with type 2 diabetes and from diabetic mice, we found opposite regulation of insulin and PDX1 mRNA; insulin was decreased in diabetes, but PDX1 was increased. This suggests that elevated PDX1 mRNA levels may be insufficient to regulate insulin. In diabetic islets, PDX1 protein was localized in the cytosol, whereas in non-diabetic controls, PDX1 was in the nucleus. In contrast, overexpression of either IL-1 receptor antagonist or shuttling-deficient PDX1 restored ß-cell survival and function and PDX1 nuclear localization. Our results show that nuclear localization of PDX1 is essential for a functional ß-cell and provides a novel mechanism of the protective effect of IL-1 receptor antagonist on ß-cell survival and function.

Continuous glucose monitoring: current clinical use.

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Prevention of diabetes: a strategic approach for individual patients.

The 'diabetes epidemic' is an important health and socioeconomic problem worldwide. Type 2 diabetes is a chronic disease with gradual deterioration in glucose metabolism which causes multiple systemic complications. Therefore, early intervention in the prediabetic stage is a valuable approach to reduce diabetes development and related complications. Many clinical trials have suggested that lifestyle intervention, including moderate-intensity exercise and diet control, and pharmacologic intervention using metformin, α-glucosidase inhibitors, thiazolidinediones, anti-obesity drugs and incretin mimics, are effective in preventing diabetes development. However, an individualized approach with careful consideration of the patient's risk status and health economics is needed to perform a successful intervention programmes. In this review, we will summarize the known evidence on treatment- and cost-effectiveness of drug and lifestyle treatment. Additionally, we will propose a strategic approach algorithm that is applicable to clinical practice.