Bidirectional association between diabetic peripheral neuropathy and vitamin B12 deficiency: Two longitudinal 9-year follow-up studies using a national sample cohort.

AIM: This study aims to investigate the association among metformin use, vit B12 deficiency, and DPN occurrence in diabetes. METHODS: This retrospective, propensity-matched cohort study was performed using National Health Insurance Service database - National Sample Cohort in South Korea. Study 1 analyzed DPN incidence according to vit B12 deficiency and study 2 analyzed vit B12 deficiency incidence according to the presence/absence of DPN. Moreover, we compared the results with respect to metformin use. RESULTS: In study 1, DPN incidence per 10000 person-year (PY) was 179.7 and 76.6 in the vit B12 and non-vit B12 deficiency groups, respectively. The adjusted HR was 1.32 (95% CI; 1.21-1.44, P < 0.05) and metformin use elicited a more significant effect of DPN occurrence in patient with vit B12 deficiency (HR: 5.76 (95% CI; 5.28-6.29). In study 2, vit B12 deficiency incidence per 10000 PY was 250.6 and 129.4 in the DPN and non-DPN groups, respectively. The adjusted HR was 2.44 (95% CI; 2.24-2.66, P < 0.05), however, metformin prescription was associated with the reduced incidence of vit B12 deficiency in DPN patients (HR 0.68 (95% CI; 0.62-0.74, P < 0.05). CONCLUSION: DPN occurrence increased in diabetes with vit B12 deficiency and the incidence of vit B12 deficiency was also high in DPN patients. However, metformin showed opposite effects in both cohorts. Further studies clarifying the causal relationship among DPN occurrence, vit B12 deficiency, and metformin use are warranted.

Analysis of clinical phenotypes of neuropathic symptoms in patients with type 2 diabetes: A multicenter study.

AIMS/INTRODUCTION: We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients. MATERIALS AND METHODS: This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients. RESULTS: Three clusters of patients with DPN were identified: severe symptoms with decreased quality of life (cluster 1, n = 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n = 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n = 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters. CONCLUSIONS: Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.

Real-world comparison of mono and dual combination therapies of metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitors using a common data model: A retrospective observational study.

ABSTRACT: The comparative effectiveness of oral hypoglycemic agents on glycemic control and chronic complications in clinical practice is unknown in Korea. This study aimed to compare glycemic control and the incidence of hypoglycemia and chronic complications among adult patients with type 2 diabetes prescribed metformin, dipeptidyl peptidase-4 inhibitors (DPP4I), and sulfonylurea (SU) as monotherapy or dual combination therapy.We retrospectively analyzed propensity-matched cohort data from 3 national university hospitals in Korea. All electronic health records were transformed into a unified Observational Medical Outcomes Partnership Common Data Model and analyzed using ATLAS, an open-source analytical tool, and R software. Glycemic control was assessed as the first observation of a reduction in glycosylated hemoglobin (HbA1c) level below 7% after prescription of the drug. Differences in the incidence of chronic complications were compared based on the first observation of each complication. Glycemic control and chronic complications were evaluated in patients who maintained the same prescription for at least 3 and 12 months, respectively.Patients who received metformin had lower hazard of reaching HbA1c levels below 7% as compared with those who received SU, and had higher hazard compared with those who received DPP4I (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.98; and HR, 1.68; 95% CI, 1.42-1.99, respectively). The incidence of hypoglycemia was significantly higher in the SU group than in the metformin and DPP4I groups (metformin vs SU; HR, 0.30; 95% CI, 0.21-0.43; SU vs DPP4I; HR, 4.42; 95% CI, 2.35-8.31). Metformin + DPP4I had similar hazard of reaching HbA1c levels below 7% compared with metformin + SU (HR, 1.19; 95% CI, 0.99-1.43) and the incidence of hypoglycemia was significantly lower in the metformin + DPP4I group (HR 0.13; 95% CI 0.05-0.30). There was no significant difference in the analysis of the occurrence of chronic complications.SU followed by metformin was effective, and both drugs showed an increased hazard of reaching HbA1c levels below 7% compared with DPP4I. Metformin + DPP4I is comparatively effective for HbA1c level reduction below 7% compared with metformin + SU. Hypoglycemia was high in the SU-containing therapy.

Influence of Glucose Fluctuation on Peripheral Nerve Damage in Streptozotocin-Induced Diabetic Rats.

BACKGROUND: It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats. METHODS: Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation. RESULTS: At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P<0.05); however, a significant difference was not observed between the DM+LAN and DM+LAN+API groups irrespective of glucose fluctuation (P>0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 µmol/mL, DM+LAN; 1.93±0.0 µmol/mL, DM+LAN+API vs. 1.25±0.04 µmol/mL, DM; P<0.05). CONCLUSION: Our study suggests that glucose control itself is more important than glucose fluctuation in the prevention of peripheral nerve damage, and intra-day glucose fluctuation has a limited effect on the progression of peripheral neuropathy in rats with diabetes.

Treatment Patterns of Type 2 Diabetes Assessed Using a Common Data Model Based on Electronic Health Records of 2000-2019.

BACKGROUND: Real-world data analysis is useful for identifying treatment patterns. Understanding drug prescription patterns of type 2 diabetes mellitus may facilitate diabetes management. We aimed to analyze treatment patterns of type 2 diabetes mellitus using Observational Medical Outcomes Partnership Common Data Model based on electronic health records. METHODS: This retrospective, observational study employed electronic health records of patients who visited Jeonbuk National University Hospital in Korea during January 2000-December 2019. Data were transformed into the Observational Medical Outcomes Partnership Common Data Model and analyzed using R version 4.0.3 and ATLAS ver. 2.7.6. Prescription frequency for each anti-diabetic drug, combination therapy pattern, and prescription pattern according to age, renal function, and glycated hemoglobin were analyzed. RESULTS: The number of adults treated for type 2 diabetes mellitus increased from 1,867 (2.0%) in 2000 to 9,972 (5.9%) in 2019. In the early 2000s, sulfonylurea was most commonly prescribed (73%), and in the recent years, metformin has been most commonly prescribed (64%). Prescription rates for DPP4 and SGLT2 inhibitors have increased gradually over the past few years. Monotherapy prescription rates decreased, whereas triple and quadruple combination prescription rates increased steadily. Different drug prescription patterns according to age, renal function, and glycated hemoglobin were observed. The proportion of patients with HbA1c ≤ 7% increased from 31.1% in 2000 to 45.6% in 2019, but that of patients visiting the emergency room for severe hypoglycemia did not change over time. CONCLUSION: Medication utilization patterns have changed significantly over the past 20 years with an increase in the use of newer drugs and a shift to combination therapies. In addition, various prescription patterns were demonstrated according to the patient characteristics in actual practice. Although glycemic control has improved, the proportion within the target is still low, underscoring the need to improve diabetes management.

Framingham Risk Score Assessment in Subjects with Pre-diabetes and Diabetes: A Cross-Sectional Study in Korea.

BACKGROUND: This study aimed to evaluate cardiovascular risk in subjects with pre-diabetes and diabetes in Korea. METHODS: In this pan-Korean, non-interventional, cross-sectional study, data were collected from medical records of 10 hospitals between November 2013 and June 2014. Subjects (aged ≥40 years) with medical records of dysglycemia and documentation of total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, and smoking status in the past 6 months were included. The primary endpoint was to determine the Framingham risk score (FRS). The relationships between FRS and cardiovascular risk factors, glycated hemoglobin, and insulin usage were determined by multiple linear regression analyses. RESULTS: Data from 1,537 subjects with pre-diabetes (n=1,025) and diabetes (n=512) were analyzed. The mean FRS (mean±standard deviation) in subjects with pre-diabetes/diabetes was 13.72±8.77. FRS was higher in subjects with diabetes than pre-diabetes (P<0.001). FRS in men with pre-diabetes was comparable to that in women with diabetes (13.80±7.37 vs. 13.35±7.13). FRS was elevated in subjects who consumed alcohol (2.66, P=0.033) and with obesity-class II (6.10, P=0.015) among subjects with diabetes (n=199), and was elevated in patients with left ventricular hypertrophy (11.10, P=0.005), those who consumed alcohol (3.06, P=0.000), were pre-obese (3.21, P=0.002), or were obesity-class I (2.89, P=0.002) among subjects with pre-diabetes (n=306) in comparison to subjects without these coexisting risk factors. CONCLUSION: Overall, Korean subjects with pre-diabetes and diabetes have an increased cardiovascular risk, which is significantly higher in those subjects with diabetes than with pre-diabetes. The present data can be used to develop measures to prevent and manage cardiovascular complications in Koreans with impaired glucose metabolism.

Effects of Gochujang (Korean Red Pepper Paste) Marinade on Polycyclic Aromatic Hydrocarbon Formation in Charcoal-Grilled Pork Belly.

Charcoal-grilling is a popular cooking method but causes the formation of polycyclic aromatic hydrocarbons (PAHs), which can be harmful to human health. Gochujang marinade is commonly used for flavoring meats during charcoal-grilling. However, the effects of this marinade on PAHs formation during charcoal-grilling are unclear. Here, we evaluated the effects of Gochujang marinade on the formation of 16 PAHs and inhibition rate of major PAHs (benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene) in charcoal-grilled pork belly. Pork belly without marinade (PBW) and marinated with Gochujang (PBG) were stored for 10 days at 9°C under vacuum conditions and then charcoal-grilled to different doneness (internal temperatures of 71°C and 81°C). Among 16 PAHs evaluated in this study, 14 PAHs were detected in charcoal-grilled pork belly, regardless of doneness. PAH formation in charcoal-grilled pork belly was higher at an internal temperature of 81°C than at 71°C (p<0.05). Initially, PBG showed reduced total PAH formation and lower percentages of three major PAHs compared with PBW. Storage increased the inhibitory effects of PBG on the 16 PAHs, and the maximum reduction in total 16 PAHs (63.06%) was observed with moderate cooking (71°C) on day 10 (p<0.05). Moreover, marinade and doneness showed a high interaction with regard to PAH contents in charcoal-grilled pork belly (p<0.05-p<0.0001). Therefore, our findings suggested that marinating pork belly with Gochujang and grilling at 71°C could reduce the formation of 16 PAHs in charcoal-grilled pork belly.

Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015).

This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study.

BACKGROUND: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). METHODS: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. RESULTS: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. CONCLUSION: This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Reference Ranges of Serum Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3: Results from a Multicenter Study in Healthy Korean Adults.

Insulin-like growth factor-I (IGF-I) plays a pivotal role in the diagnosis and treatment of growth hormone (GH) excess or deficiency. The GH study group of the Korean Endocrine Society aims to establish the Korean reference ranges of serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) and assess the relationship between IGF-I and IGFBP-3 and clinical parameters. Fasting serum was collected from healthy Korean adults at health promotion centers of five hospitals nationwide. Serum IGF-I and IGFBP-3 were measured via an immunoradiometric assay using a DSL kit (Diagnostic Systems Laboratories). Serum samples from 354 subjects (180 male, 174 female) were analyzed based on sex at 10-year intervals from 21 to 70 years. IGF-I levels were inversely correlated with age. After adjustment of age, the IGF-I/IGFBP-3 ratio was significantly negatively associated with blood pressure and free thyroxine and positively associated with weight, hemoglobin, creatinine, alanine transferase, fasting glucose, and thyroid stimulating hormone. Therefore, age- and sex-specific reference ranges of serum IGF-I and IGFBP-3 can be efficient in evaluating GH excess or deficiency in Korean population.

Effects of a Lifestyle-Modification Program on Blood-Glucose Regulation and Health Promotion in Diabetic Patients: A Randomized Controlled Trial.

BACKGROUND: We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. METHODS: Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. RESULTS: HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). CONCLUSION: Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.

Non-glucose risk factors in the pathogenesis of diabetic peripheral neuropathy.

In this review, we consider the diverse risk factors in diabetes patients beyond hyperglycemia that are being recognized as contributors to diabetic peripheral neuropathy (DPN). Interest in such alternative mechanisms has been encouraged by the recognition that neuropathy occurs in subjects with metabolic syndrome and pre-diabetes and by the reporting of several large clinical studies that failed to show reduced prevalence of neuropathy after intensive glucose control in patients with type 2 diabetes. Animal models of obesity, dyslipidemia, hypertension, and other disorders common to both pre-diabetes and diabetes have been used to highlight a number of plausible pathogenic mechanisms that may either damage the nerve independent of hyperglycemia or augment the toxic potential of hyperglycemia. While pathogenic mechanisms stemming from hyperglycemia are likely to be significant contributors to DPN, future therapeutic strategies will require a more nuanced approach that considers a range of concurrent insults derived from the complex pathophysiology of diabetes beyond direct hyperglycemia.

Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats.

BACKGROUND: Metformin is widely marketed medication for the treatment of diabetes, but its pharmacological effect on diabetic peripheral neuropathy remains unclear. In this study, the effect of metformin on peripheral nerves in diabetic rats was investigated using diverse neuronal parameters of nerve fibers. METHODS: Rats were assigned to one of four groups (n=7 to 10 per group): normal, diabetes mellitus (DM), DM+metformin (100 mg/kg), and DM+alpha lipoic acid (ALA, 100 mg/kg). DM was induced by streptozotocin/high-fat diet (STZ/HFD). After 12 weeks, the sensory thresholds to mechanical and heat stimuli were assessed. Repeated sensory tests, immunofluorescence microscopic comparison of peripheral nerves, and biochemical blood analysis were performed after 24 weeks. RESULTS: Both DM+metformin and DM+ALA groups showed similar trends to diverse sensory tests at 24 weeks compared to DM group although the degree of change were different according to the stimulated senses. There was no significant difference in the comparison of the intraepidermal nerve fiber density (IENFD) of peripheral nerves between the DM+metformin and DM+ALA groups (11.83±0.07 fibers/mm vs. 12.37±1.82 fibers/mm, respectively). Both groups showed preserved IENFD significantly compared with DM group (8.46±1.98 fibers/mm, P<0.05). Sciatic nerve morphology of the experimental animals showed a similar trend to the IENFD, with respect to axonal diameter, myelin sheath thickness, and myelinated fiber diameter. CONCLUSION: Metformin has beneficial pharmacological effects on the preservation of peripheral nerves in diabetic rats and its effects are comparable to those of ALA.

The association between cardiac autonomic neuropathy and heart function in type 2 diabetic patients.

Aim: Cardiac autonomic neuropathy (CAN) is a common and important chronic complication in diabetic patients. Heart failure resulting from cardiomyopathy is also a lethal complication in diabetic patients. However, data showing the exact association between CAN and heart failure in diabetic patients are relatively scarce. Therefore, our study aimed to determine the association between the parameters assessing CAN and heart function in diabetic patients.Method: The medical records of type 2 diabetic patients who underwent an autonomic function test with heart rate variability (HRV) and echocardiography were reviewed from January 2018 to December 2018. A total of 100 type 2 diabetic patients were included, and the association between the parameters assessing CAN and heart function was analysed.Results: Among the 100 analysed patients, 65 were diagnosed with CAN and 26 showed diastolic dysfunction. Moreover, 19 (73.1%) diabetic patients with diastolic dysfunction were complicated with CAN. The occurrence of diastolic dysfunction was higher in diabetic patients with CAN than in diabetic patients without CAN (29.2% vs 20.0%, p < 0.05), and the occurrence of CAN was higher in diabetic patients with diastolic dysfunction than in patients without diastolic dysfunction (73.1% vs 62.2%, p < 0.05). However, there were no significant associations between HRV parameters and heart function.Conclusion: We demonstrated that diastolic dysfunction is more common in diabetic patients complicated with CAN than in diabetic patients without CAN, although several diabetic patients without diastolic dysfunction are also diagnosed with CAN. Moreover, further studies about the long-term serial monitoring of heart function according to the progression of CAN are required to confirm the exact association between CAN and heart function.

γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial.

BACKGROUND: This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). METHODS: This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). RESULTS: Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments. CONCLUSION: GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

The Degree of Hyperglycemia Excursion in Patients of Kidney Transplantation (KT) or Liver Transplantation (LT) Assessed by Continuous Glucose Monitoring (CGM): Pilot Study.

OBJECTIVE: This study used a continuous glucose monitoring system (CGMS) to investigate the glucose profiles and assess the degree of hyperglycemic excursion after kidney or liver transplantation during the early period after operation. METHODS: Patients to whom a CGMS was attached during a postoperative period of approximately one month after transplantation were included. The CGM data of 31 patients including 24 with kidney transplantation (KT) and seven with liver transplantation (LT) were analyzed. RESULTS: Hyperglycemia over 126 mg/dL (fasting) or 200 g/dL (postprandial) occurred in 42.1% (8/19) and 16.7% (1/6) of KT and LT patients, respectively, during this early period after transplantation, except for patients with preexisting diabetes (5 KT, 1 LT). The average mean amplitude of glycemic excursion (MAGE) and mean absolute glucose (MAG) levels were 91.18 ± 26.51 vs. 65.66 ± 22.55 (P < 0.05) and 24.62 ± 7.78 vs. 18.18 ± 7.07 (P < 0.05) in KT vs. LT patients, respectively, in patients without preexisting DM or PTDM patients who showed normal glucose levels. Average increase from the lowest level to the peak glucose value was higher in KT patients than LT patients (P < 0.05). Conclusions. The transplanted organ also needs to be considered as an important factor affecting glucose control and the occurrence of more severe glucose excursions in patients who receive transplantation although immunosuppression agents are well-known important factors; however, our study was limited to the early posttransplantation period. Further studies involving CGM follow-up at regular intervals based on the time since transplantation are needed.

Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea.

BACKGROUND: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia. RESULTS: The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. -0.9±6.0 kg, P=0.011). CONCLUSION: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Predictive Factors for Efficacy of AST-120 Treatment in Diabetic Nephropathy: a Prospective Single-Arm, Open-Label, Multi-Center Study.

BACKGROUND: Removal of uremic toxins such as indoxyl sulfate by AST-120 is known to improve renal function and delay the initiation of dialysis in patients with advanced chronic kidney disease. However, it is unclear whether the addition of AST-120 to conventional treatments is effective in delaying the progression of renal dysfunction in patients with diabetic nephropathy. METHODS: A total of 100 patients with type 2 diabetes and renal dysfunction (serum creatinine levels ranging from 1.5 to 3.0 mg/dL) were recruited from eight centers in Korea and treated with AST-120 (6 g/day) for 24 weeks. The primary endpoint was improvement in renal function measured as the gradient of the reciprocal serum creatinine level (1/sCr) over time (i.e., the ratio of 1/sCr time slope for post- to pre-AST-120 therapy). A response was defined as a ratio change of the regression coefficient of 1/sCr ≤ 0.90. RESULTS: Renal function improved in 80.3% of patients (61/76) after 24 weeks of AST-120 treatment. There were no differences between responder and non-responder groups in baseline characteristics except for diastolic blood pressure (73.5 ± 9.5 mmHg in the responder group vs. 79.3 ± 11.1 mmHg in the non-responder group; P = 0.046). Serum lipid peroxidation level decreased significantly in the responder group (from 2.25 ± 0.56 µol/L to 1.91 ± 0.72 µol/L; P = 0.002) but not in the non-responder group. CONCLUSION: The addition of AST-120 to conventional treatments may delay the progression of renal dysfunction in diabetic nephropathy. The antioxidant effect of AST-120 might contribute to improvement in renal function.