Type II Diabetes Research Articles

Customized Integrated Management for Non-Insulin Dependent Diabetes Mellitus (NIDDM) and its Complications: Literature Review and Recommendations for the Future Policy Decisions

Customized Integrated Management for Non-Insulin Dependent Diabetes Mellitus (NIDDM) and its Complications: Literature Review and Recommendations for the Future Policy Decisions

Great leap forward famine exposure and urban-rural migration convolute the modern prevalence of diabetes in China

BackgroundAlthough evidence from birth cohort analysis has indicated the metabolic risk of early-life exposure to the Great Leap Forward Famine (GLFF) in China, three confounding effects, including the exposure windows, aging, and geographical variations in famine severity, have been brought to debates for a decade. This study aimed to address these confounding effects and extensively examine how GLFF exposure is associated with diabetes risk in mid-to-late life and its interaction with urban-rural migration.MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed with age-stratification and stepped wedge approaches. Weighted prevalence and multivariable logistic regression were used to investigate the effects of GLFF exposure and urban-rural migration on mid-to-late life diabetes risk and the interaction between GLFF exposure and urban-rural migration. Birth provinces were controlled as a fixed effect to account for variations in famine severity across provinces.ResultsCompared to those who were never exposed to GLFF, fetal GLFF exposure was associated with a higher risk of adult-onset diabetes after controlling for provinces, demographics, and health statuses. Yet, after adding the proxy of childhood growth environments into the model, fetal exposure to GLFF was not significantly associated with adult-onset diabetes risk (OR = 1.22, p = 0.10), compared to those who were never exposed to GLFF. Across the three age-stratification groups, static urban residents, in general, had a higher risk of diabetes compared to static rural residents. Interaction effects between GLFF exposure and urban-rural migration were insignificant across all three age-stratification groups.ConclusionFetal exposure to GLFF might have a traceable effect on adult-onset diabetes risk. Yet, the growth environment and urban lifestyle outweigh and further confound the impact of GLFF exposure on adult-onset diabetes risk.

Determining Risk Factors for Detachment After Endothelial Keratoplasties: Nine-Year Review of a Single Institution.

To determine roles of patient history, donor tissue characteristics, tissue preparation methods, and surgeon technique for graft detachment requiring rebubbling after Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures. Retrospective analysis of all eyes undergoing first-time DSAEK or DMEK at the study institution between 2013 and 2022. Data were collected regarding recipients' history, donors' medical history, tissue preparation methods, intraoperative details, and postoperative clinical outcomes. Multivariate statistical analysis was conducted to identify risk factors for graft detachment necessitating rebubbling. Of 1240 eyes meeting inclusion criteria, 746 (60.2%) underwent DSAEK, and 494 (39.8%) underwent DMEK. DSAEK procedures had 12.5% rebubbling rate, whereas DMEK procedures had 18.4% rebubbling rate (P = 0.005). Sub50-DSAEK (<50 μm) grafts had 16.0% rebubble rate, whereas sub100-DSAEK (51-99 μm) and >100 μm DSAEKs had rebubble rate of 9.9% and 9.5%, respectively (P = 0.006). Significant risk factors for DSAEK graft detachment included history of retinal surgery (OR = 2.59), preloaded tissue (OR = 2.70), forceps insertion (OR = 2.33), use of sub50-DSAEK lenticules versus sub100-DSAEK (OR = 2.44) and >100 μm DSAEK (OR = 2.38) lenticules, and donor history of noninsulin-dependent diabetes mellitus (OR = 4.18). DMEK risk factors included recipient history of cancer (OR = 2.51) and use of higher SF6 gas concentration (OR = 1.09). Although rebubbled DMEK eyes had comparable refractive outcomes to nonrebubbled eyes (P >0.05), rebubbled DSAEK eyes had worse refractive outcomes at all time points (P < 0.05). Graft detachments in DSAEK and DMEK are influenced by various factors, including donor tissue characteristics, tissue preparation, and surgical technique. Identifying and understanding these factors can potentially improve postoperative outcomes.

Mangiferin Induces Post-Implant Osteointegration in Male Diabetic Rats.

Background and Objectives: Hyperglycemia is known to undermine the osteointegration process of implants. In this study, the effects of mangiferin (MF) on the post-implant osteointegration process in a type-II diabetes model were investigated molecularly and morphologically. Materials and Methods: Sprague Dawley male rats were divided into three groups: control, diabetes, and diabetes + MF. All animals were implanted in their tibia bones on day 0. At the end of the 3-month experimental period, the animals' blood and the implant area were isolated. Biochemical measurements were performed on blood samples and micro-CT, qRT-PCR, histological, and immunohistochemical measurements were performed on tibia samples. Results: MF significantly improved the increased glucose, triglyceride-VLDL levels, and liver enzymes due to diabetes. By administering MF to diabetic rats, the osteointegration percentage and bone volume increased while porosity decreased. DKK1 and BMP-2 mRNA expressions and OPN, OCN, and OSN mRNA-protein expressions increased by MF administration in diabetic rats. Additionally, while osteoblast and osteoid surface areas increased with MF, osteoclast and eroded surface areas decreased. Conclusions: The findings of our study indicate that MF will be beneficial to the bone-repairing process and osteointegration, which are impaired by type-II diabetes.

Apremilast as a Potential Targeted Therapy for Metabolic Syndrome in Patients with Psoriasis: An Observational Analysis.

Psoriasis (PsO) is a chronic inflammatory dermatosis that often presents with erythematous, sharply demarcated lesions. Although psoriasis is primarily a dermatological disease, its immune-mediated pathogenesis produces systemic effects and is closely associated with various comorbid conditions such as cardiovascular disease (CVD), metabolic syndrome (MetS), and diabetes mellitus type II (DMII). Apremilast, an oral phosphodiesterase 4 (PDE-4) inhibitor, has shown promise in treating moderate-to-severe psoriasis and is associated with potential cardiometabolic benefits. In a 12-month prospective observational study involving 137 patients with moderate-to-severe psoriasis, we assessed changes in psoriasis clinimetric scores and metabolic profiles from baseline (T0) to 52 weeks (T1) to evaluate the efficacy of apremilast. After 52 weeks of apremilast treatment, we documented a statistically significant decrease in low-density lipoprotein (LDL) and total cholesterol, triglycerides, and glucose levels. Our findings even suggest a potential synergistic effect among patients treated with apremilast, alongside concomitant statin and/or insulin therapy. Although the results of our study must be validated on a larger scale, the use of apremilast in the treatment of psoriatic patients with cardio-metabolic comorbidities yields promising results.

Sclerostin antibody corrects periodontal disease in type 2 diabetic mice.

Type 2 diabetes (T2D) is on the rise worldwide and is associated with various complications in the oral cavity. Using an adult-onset diabetes preclinical model, we demonstrated profound periodontal alterations in T2D mice, including inflamed gingiva, disintegrated periodontal ligaments (PDLs), marked alveolar bone loss, and unbalanced bone remodeling due to decreased formation and increased resorption. Notably, we observed elevated levels of the Wnt signaling inhibitor sclerostin in the alveolar bone of T2D mice. Motivated by these findings, we investigated whether a sclerostin-neutralizing antibody (Scl-Ab) could rescue the compromised periodontium in T2D mice. Administering Scl-Ab subcutaneously once a week for 4 weeks, starting 4 weeks after T2D induction, led to substantial increases in bone mass. This effect was attributed to the inhibition of osteoclasts and promotion of osteoblasts in both control and T2D mice, effectively reversing the bone loss caused by T2D. Furthermore, Scl-Ab stimulated PDL cell proliferation, partially restored the PDL fibers, and mitigated inflammation in the periodontium. Our study thus established a T2D-induced periodontitis mouse model characterized by inflammation and tissue degeneration. Scl-Ab emerged as a promising intervention to counteract the detrimental effects of T2D on the periodontium, exhibiting limited side effects on other craniofacial hard tissues.

In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies.

Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase's active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes.

Autoantibodies to truncated GAD(96-585) antigen stratify risk of early insulin requirement in adult-onset diabetes.

We investigated whether characterisation of full-length (f-)GADA responses could identify early insulin requirement in adult-onset diabetes. In 179 f-GADA positive participants diagnosed with type 2 diabetes, we assessed associations of truncated (t-)GADA positivity, f-GADA IgG subclasses, and f-GADA affinity with early insulin requirement (<5 years), type 1 diabetes genetic risk score (T1D GRS), and C-peptide. t-GADA positivity was lower in f-GADA positive without early insulin in comparison to f-GADA positive type 2 diabetes requiring insulin within 5 years, and type 1 diabetes (75% vs. 91% and 95% respectively, p<0.0001). t-GADA positivity (in those f-GADA positive) identified a group with a higher type 1 diabetes genetic susceptibility (mean T1D GRS 0.248 vs. 0.225, p=0.003), lower C-peptide (1156 pmol/L vs. 4289 pmol/L, p=1x10-7), and increased IA-2A positivity (23% vs. 6%, p=0.03). In survival analysis, t-GADA positivity was associated with early insulin requirement compared with those only positive for f-GADA, independently from age of diagnosis, f-GADA titre and duration of diabetes [adjusted HR 5.7 (95% CI 1.4, 23.5), p=0.017]. The testing of t-GADA in f-GADA positive individuals with type 2 diabetes identifies those who have genetic and clinical characteristics comparable to type 1 diabetes and stratifies those at higher risk of early insulin requirement.

Equilibrium solubility and mathematical modelling of glibenclamide in cosolvent mixtures of glycols and alcohols

ABSTRACT Glibenclamide (GBN) is a commonly used oral medication for treating type-II diabetes that acts by reducing high blood sugar levels. The effectiveness of GBN depends on the quality of the product. The quality is influenced by the solubility properties of a drug. This study aimed to measure the solubility of GBN in various solvent mixtures including some glycols and alcohols. The solubility was determined using a shake-flask method at 298.2 K under atmospheric pressure. The results showed that GBN had the highest solubility in ethylene glycol monomethyl ether and alcohol mixtures compared to the other tested glycols.

Potential Antidiabetic Activity of β-sitosterol from Zingiber roseum Rosc. via Modulation of Peroxisome Proliferator-activated Receptor Gamma (PPARγ).

To evaluate the antidiabetic potential of β-sitosterol from Zingiber roseum. Diabetes mellitus is a cluster of metabolic disorders, and 90% of diabetic patients are affected with Type II diabetes (DM2). For the treatment of DM2, thiazolidinedione drugs (TZDs) were proposed, but recent studies have shown that TZDs have several detrimental effects, such as weight gain, kidney enlargement (hypertrophy), fluid retention, increased risk of bone fractures, and potential harm to the liver (hepatotoxicity). That is why a new molecule is needed to treat DM2. The current research aimed to assess the efficacy of β-Sitosterol from methanolic extract of Zingiber roseum in managing diabetes via PPARγ modulation. Zingiber roseum was extracted using methanol, and GC-MS was employed to analyze the extract. Through homology modeling, PPARγ structure was predicted. Molecular docking, MD simulation, free binding energies, QSAR, ADMET, and bioactivity and toxicity scores were all used during the in-depth computer-based research. Clinically, agonists of synthetic thiazolidinedione (TZDs) have been used therapeutically to treat DM2, but these TZDs are associated with significant risks. Hence, GC-MS identified phytochemicals to search for a new PPAR-γ agonist. Based on the in-silico investigation, β-sitosterol was found to have a higher binding affinity (-8.9 kcal/mol) than standard drugs. MD simulations and MMGBSA analysis also demonstrated that β-sitosterol bound to the PPAR-γ active site stably. It can be concluded that β-sitosterol from Z. roseum attenuates Type-II diabetes by modulating PPARγ activity.

Evaluation of pancreatic iodine uptake and related influential factors in multiphase dual-energy CT.

To establish normative values and identify potential factors influencing pancreatic iodine uptake using dual-energy CT (DECT). This retrospective study included participants without pancreatic diseases undergoing DECT at two institutions with different platforms. Their protocols both included arterial phase (AP), portal venous phase (PP), and equilibrium phase (EP), defined as 35 s-40 s, 60 s-70 s, and 150 s-180 s after injection of contrast agent, respectively. Both iodine concentration (IC) and normalised IC (NIC) were measured. Demographic features, local measurements of the pancreas and visceral fat area (VFA) were considered as potential factors influencing iodine uptake using multivariate linear regression analyses. A total of 562 participants (median age 58 years [interquartile range: 47-67], with 282 men) were evaluated. The mean IC differed significantly between two institutions (all p < 0.001) across three contrast-enhanced phases, while the mean NIC showed no significant differences (all p > 0.05). The mean values of NIC were 0.22 at AP, 0.43 at PP and 0.45 at EP. NICAP was independently affected by VFA (β = 0.362, p < 0.001), smoking (β = -0.240, p = 0.001), and type-II diabetes (β = -0.449, p < 0.001); NICPP by VFA (β = -0.301, p = 0.017) and smoking (β = -0.291, p < 0.001); and NICEP by smoking (β = -0.154, p = 0.10) and alcohol consumption (β = -0.350, p < 0.001) with statistical power values over 0.81. NIC values were consistent across institutions. Abdominal obesity, smoking, alcohol consumption, and diabetes are independent factors influencing pancreatic iodine uptake. This study has provided reference normative values, influential factors and effective normalisation methods of pancreatic iodine uptake in multiphase dual-energy CT for future studies in this area as a new biological marker. Evaluation of pancreatic iodine uptake measured by dual-energy CT is a promising method for future studies. Abdominal obesity, smoking, alcohol consumption, diabetes, and sex are independent factors influencing pancreatic iodine uptake. Utility of normalised iodine concentration is necessary to ensure the consistency across different institutions.

Outpatient insulin use in type 2 diabetes mellitus and acute respiratory distress syndrome outcomes: A retrospective cohort study.

The impact of type 2 diabetes mellitus (T2DM) on acute respiratory distress syndrome (ARDS) is debatable. T2DM was suspected to reduce the risk and complications of ARDS. However, during coronavirus disease 2019 (COVID-19), T2DM predisposed patients to ARDS, especially those who were on insulin at home. To evaluate the impact of outpatient insulin use in T2DM patients on non-COVID-19 ARDS outcomes. We conducted a retrospective cohort analysis using the Nationwide Inpatient Sample database. Adult patients diagnosed with ARDS were stratified into insulin-dependent diabetes mellitus (DM) (IDDM) and non-insulin-dependent DM (NIDDM) groups. After applying exclusion criteria and matching over 20 variables, we compared cohorts for mortality, duration of mechanical ventilation, incidence of acute kidney injury (AKI), length of stay (LOS), hospitalization costs, and other clinical outcomes. Following 1:1 propensity score matching, the analysis included 274 patients in each group. Notably, no statistically significant differences emerged between the IDDM and NIDDM groups in terms of mortality rates (32.8% vs 31.0%, P = 0.520), median hospital LOS (10 d, P = 0.537), requirement for mechanical ventilation, incidence rates of sepsis, pneumonia or AKI, median total hospitalization costs, or patient disposition upon discharge. Compared to alternative anti-diabetic medications, outpatient insulin treatment does not appear to exert an independent influence on in-hospital morbidity or mortality in diabetic patients with non-COVID-19 ARDS.

Chitosan-modified dihydromyricetin liposomes promote the repair of liver injury in mice suffering from diabetes mellitus

Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration–time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-β1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.

Insulin dependence negatively impacts outcomes in anterior cervical discectomy with fusions: a 10-year retrospective analysis

BACKGROUND CONTEXTAlthough anterior cervical discectomy and fusion (ACDF) procedures for cervical spine disease have been increasing amid a growing diabetic patient population, there is a paucity of literature focusing on insulin-dependence as a risk-factor for postoperative ACDF complications. PURPOSETo evaluate the differential impact of insulin dependence on perioperative outcomes including total length of stay, surgical, and medical complications within thirty days following ACDF. STUDY DESIGN/SETTINGA retrospective cohort, large multicenter database study. PATIENT SAMPLEThe American College of Surgeons National Surgical Quality Improvement Program database was queried to retrospectively identify patients who had undergone ACDF between 2011 and 2021 using the Current Procedural Terminology code 22551. OUTCOME MEASURESPerioperative surgical and medical complications. METHODSThe study population was divided into 3 groups 1) insulin-dependent diabetes mellitus (IDDM), 2) noninsulin-dependent diabetes mellitus (NIDDM), and 3) no diabetes mellitus (non-DM). One-way analysis of variance for continuous variables and chi-square tests for categorical variables were used to identify differences in perioperative variables between the 3 groups. Multivariable logistic regression analysis assessed the effect of diabetes mellitus status on postoperative medical and surgical outcomes. RESULTSA total of 85,758 ACDF procedures were identified between 2011 and 2021, of which 5,178 were IDDM, 9,652 were NIDDM, and 70,982 were non-DM. The rates of surgical and medical complication varied between the 3 groups. IDDM patients had the highest rates of at least one medical complication (6.1%). Only IDDM increased the risk for medical complications (OR: 1.320, 95% CI [1.144–1.518]) and extended hospital length of stay (LOS) (OR: 1.244, 95% CI [1.071–1.441]) following a multivariate logistic regression analysis. CONCLUSIONPatients with IDDM were at an increased risk for postoperative medical complications and extended hospital LOS. Personalized postoperative management, guided by risk assessment is indicated for this population. These findings can be used to improve risk stratification and informed consent for DM patients who are insulin dependent.

Development, characterization, and evaluation of polymer-based hydrogel membrane patches for intestinal delivery of gliclazide

ABSTRACT The study aimed to develop, characterize, and evaluate matrix-type oral bi-layered mucoadhesive hydrogel membrane patches for the intestinal delivery of gliclazide. Surface pH, drug content, thickness, folding endurance, moisture content, water vapor transmission rate, and swellability of hydrogel membrane patches were found satisfactory. These patches were characterized by SEM, DSC, and FT-IR spectroscopy. In-vitro gliclazide release from these hydrogel membrane patches was sustained over 8 h. Ex-vivo study demonstrated good mucoadhesion of these hydrogel membrane patches. Therefore, these matrix-type oral bi-layered mucoadhesive-natured PNIPAM-co-MM/chitosan made-hydrogel membrane patches for intestinal delivery of gliclazide can be effectively used in type-II diabetes mellitus management.

In Vitro Analysis of Camellia sinensis Leaf Extract Against Diabetes Mellitus.

Diabetes mellitus (DM) poses a significant global health challenge, with its prevalence steadily increasing. Natural compounds derived from plants have garnered attention for their potential therapeutic effects in managing this metabolic disorder. Camellia sinensis, commonly known as tea, is rich in bioactive compounds exhibiting various pharmacological properties. This study investigates the potential anti-diabetic activity of C. sinensis leaf extract through in vitro analysis. Camella sinensisleaf extract was prepared by grinding the plant's leaf into a powder, mixing it with distilled water, and heating. The antidiabetic activity was assessed through α-Amylase and α-Glucosidase inhibitory assays, employing varying concentrations of the plant extract. Molecular docking analysis utilized Autodock 1.5.6 software (The Scripps Research Institute, California, US)to predict ligand-receptor interactions, guiding subsequent experimental validation. Camella sinensisleaf extract exhibited high phenolic content, suggesting potential in managing hyperglycemia. Tannins may aid glucose absorption and inhibit adipogenesis, making them promising for non-insulin-dependent DM (NIDDM). Terpenoids, with antioxidant activity, inhibit advanced glycation. Saponins and steroids were absent. Molecular docking revealed residues like IR, IRS1, and AS160 with significant impact on α-Amylase and α-Glucosidase, comparable to metformin. The findings of this study highlight the promising potential of C. sinensis leaf extract in managing hyperglycemia associated with DM. The high phenolic content aids in glucose regulation. Specifically, the presence of tannins suggests a potential role in modulating glucose absorption and inhibiting adipogenesis, which could be particularly beneficial for individuals with NIDDM.These findings provide valuable insights into the molecular mechanisms underlying the potential therapeutic efficacy of C. sinensis leaf extract against DM, paving the way for further research and development of novel therapeutic interventions in diabetes management.

Uncontrolled diabetes mellitus and the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans.

7551 Background: Studies have shown that, independent of obesity, the metabolic effects of diabetes mellitus (DM) promote the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). However, it is unclear whether glycemic control is associated with MGUS progression in DM patients. We aimed to evaluate the association between poor glycemic control, measured by HbA1c &gt;6.5%, and progression. Methods: Patients diagnosed with MGUS from 1999-2021 in the Veterans Health Administration (VHA) were identified using a published natural language processing (NLP)-based algorithm. We focused on patients whose MGUS subtype was IgG, IgA, or light chain. We excluded patients lacking body weight measurements from the time of MGUS diagnosis to the end of follow-up to ensure receiving care in the VHA. We further excluded patients with extended gaps &gt;1 year between HbA1c measurements. Time-varying HbA1c measurements during the follow-up, evaluated at 1-day intervals and categorized into uncontrolled (HbA1c &gt;6.5%) or controlled (≤6.5%) DM was the exposure variable. Progression of MGUS to MM was also confirmed by a published NLP algorithm. The association between the time-varying controlled/uncontrolled DM and progression was estimated by multivariable-adjusted hazard ratio (aHR) with death as a competing event. The covariates included sex, race, MGUS subtype as well as age, body mass index, monoclonal protein level, Charlson Comorbidity Index, DM medication, and DM type (type 1, type 2 with insulin-dependency status, type 2 without insulin-dependency status), all at MGUS diagnosis. Same analysis was conducted in a subgroup of patients with non-insulin dependent DM type 2 (NIDDMT2) without insulin use between MGUS diagnosis and the end of follow-up. Results: After applying inclusion and exclusion criteria, we identified 9,682 patients with both DM and MGUS. The multivariable analysis revealed a positive association between poor glycemic control and MM progression (see Table): (aHR 1.27, 95% CI 1.13-1.42). In NIDDMT2 without insulin use (n=3,498), poor glycemic control was associated with MM progression (aHR 1.81; 95% CI 1.57-2.10). Conclusions: For patients with DM and MGUS, the risk of MGUS progression to MM was 27% higher in uncontrolled DM and 81% higher in patients with NIDDMT2. This finding highlights a modifiable risk factor for MM progression in MGUS patients. Future studies should examine if interventions to enhance glycemic control could potentially reduce MGUS progression.

Impact of Diabetes in Patients With Acute Myocardial Infarction Undergoing Coronary Artery Bypass Surgery Within 48 Hours

Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.

Developing Research for Five Subtypes of Diabetes with Specific Characteristics

Recently, sub-classifications for adult-onset diabetes have been presented based on cluster analysis. There are 5 exclusive subtypes, with clusters ranging from 1 to 5: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD), respectively. The related variables known include GAD antibody, age at diagnosis, BMI, HbA1c, and HOMA2-B and HOMA2-IR. From the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the numerical numbers of the 5 subtypes are 241-1594-914-1595-2673, respectively. The prevalence percentages for the 5 subtypes in 3 countries are as follows: Japan: 5.4-19.0-7.2-28.9-39.5, Germany: 22.0-3.0-11.0-29.0-35.0, and Finland: 9.9-8.9-11.2-22.8-47.3, respectively.

Clinical and functional characterization of a novel KCNJ11 (c.101G > A, p.R34H) mutation associated with maturity-onset diabetes mellitus of the young type 13.

This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic β-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.