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.

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.

Common Salivary Protein 1 in Saliva of Diabetes Patients (II).

BACKGROUND: Human common salivary protein 1 (CSP1) is one of a variety of molecules in saliva but its function remains to be determined. The gold standard method for diagnosis of diabetes mellitus (DM) is to check levels of glucose or HbA1C in plasma or serum. The purpose of this study was to examine whether Salivary CSP1 concentration would be useful alternative for DM diagnosis. METHODS: The qualities of monoclonal antibodies (mAbs) to recombinant human CSP1 (rhCSP1) were tested by western blotting (WB) and immunohistochemistry. A sandwich ELISA was fabricated with the qualified capture and detector mAbs for measurement of CSP1 level in saliva. CSP1 levels of healthy adults and DM patients were measured by the sandwich ELISA and their results were statistically analyzed by Student's t-test. The receiver operating characteristic (ROC) curve was constructed and the area under the curve (AUC) was calculated. RESULTS: The tested mAbs recognized a 27-kDa CSP1 of saliva in WB and stained only a salivary gland in immunohistochemistry. Pearson's correlation coefficient with standard curve between OD450nm value vs. CSP level showed good linearity (r2 = 0.995). The median values (25th to 75th percentiles) of saliva CSP1 in 10 healthy adults and 18 DM patients using the sandwich ELISA were 3.92 µg/mL (3.15 - 4.02) and 4.35 µg/mL (3.94 - 5.11), respectively. Statistically, there was a significant difference of CSP1 level in two groups (p = 0.026). The sensitivity value of CSP1 was 64.71 while the specificity value was 88.89 with 0.784 of AUC (p = 0.003). These results suggested that the fabricated sandwich ELISA was a good diagnostic test tool for discriminating DM patients from healthy individuals. CONCLUSIONS: The present data showed a significant increase of CSP1 levels for DM patients compared with control group, indicating that CSP1 level in saliva could be used as a potential biomarker of detection or screening of DM patients. However, further studies are necessary to provide scientific and clinical validation.

Factors influencing psychological insulin resistance in type 2 diabetes patients.

AIMS: This descriptive, exploratory, correlational analysis investigated patients with type 2 diabetes and their diabetes knowledge, depression, diabetes-management self-efficacy, and social support and sought to determine the effects of these factors on psychological insulin resistance among type 2 diabetes patients in South Korea. METHODS: This descriptive cross-sectional study included 136 patients with type 2 diabetes who visited an endocrinology clinic. A structured questionnaire and electronic medical records were used to collect data regarding demographic and disease-related characteristics as well as scores on the Diabetes Knowledge Tests, Center for Epidemiologic Studies Depression Scale, Diabetes Management Self-efficacy Scale, Social Support Scale, and Psychological Insulin Resistance Scale, between September and December 2017. Data were analysed using descriptive statistics, independent t-tests, a one-way ANOVA, Pearson's correlation coefficient, and stepwise multiple regression. RESULTS: The total score for psychological insulin resistance was 60.92 ± 14.75 of a maximum of 90. Stepwise multiple regression showed that diabetes knowledge, diabetes-management self-efficacy, social support, absence of diabetes complications, and depression explained 38.6% of the variance in psychological insulin resistance. CONCLUSION: Diabetes knowledge was found to have the largest influence on psychological insulin resistance, followed by social support, absence of complications, depression, and diabetes-management self-efficacy. Development of interventions that consider all these factors is required, and the effects of such interventions should be tested through further research.

Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness.

Despite the rapidly increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D), few treatment modalities are currently available. We investigated the hepatic effects of the novel thiazolidinedione (TZDs), lobeglitazone (Duvie) in T2D patients with NAFLD. We recruited drug-naïve or metformin-treated T2D patients with NAFLD to conduct a multicenter, prospective, open-label, exploratory clinical trial. Transient liver elastography (Fibroscan®; Echosens, Paris, France) with controlled attenuation parameter (CAP) was used to non-invasively quantify hepatic fat contents. Fifty patients with CAP values above 250 dB/m were treated once daily with 0.5 mg lobeglitazone for 24 weeks. The primary endpoint was a decline in CAP values, and secondary endpoints included changes in components of glycemic, lipid, and liver profiles. Lobeglitazone-treated patients showed significantly decreased CAP values (313.4 dB/m at baseline vs. 297.8 dB/m at 24 weeks; P = 0.016), regardless of glycemic control. Lobeglitazone improved HbA(1C) values (7.41% [57.5 mM] vs. 6.56% [48.2 mM]; P < 0.001), as well as the lipid and liver profiles of the treated patients. Moreover, multivariable linear regression analysis showed that hepatic fat reduction by lobeglitazone was independently associated with baseline values of CAP, liver stiffness, and liver enzymes, and metformin use. Lobeglitazone treatment reduced intrahepatic fat content, as assessed by transient liver elastography, and improved glycemic, liver, and lipid profiles in T2D patients with NAFLD. Further randomized controlled trials using liver histology as an end point are necessary to evaluate the efficacy of lobeglitazone for NAFLD treatment.

Comparison of sensory tests and neuronal quantity of peripheral nerves between streptozotocin (STZ)-induced diabetic rats and paclitaxel (PAC)-treated rats.

Although diabetic peripheral neuropathy (DPN) and chemotherapy-induced peripheral neuropathy (CIPN) are different disease entities, they share similar neuropathic symptoms that impede quality of life for these patients. Despite having very similar downstream effects, there have been no direct comparisons between DPN and CIPN with respect to symptom severity and therapeutic responses. We compared peripheral nerve damage due to hyperglycemia with that caused by paclitaxel (PAC) treatment as represented by biochemical parameters, diverse sensory tests, and immunohistochemistry of cutaneous and sciatic nerves. The therapeutic effects of alpha-lipoic acid and DA-9801 were also compared in the two models. Animals were divided into seven groups (n = 7-10) as follows: normal, diabetes (DM), DM + alpha-lipoic acid 100 mg/kg (ALA), DM + DA-9801 (100 mg/kg), paclitaxel-treated rat (PAC), PAC + ALA (100 mg/kg), and PAC + DA-9801 (100 mg/kg). The sensory thresholds of animals to mechanical, heat, and pressure stimuli were altered by both hyperglycemia and PAC when compared with controls, and the responses to sensory tests were different between both groups. There were no significant differences in the biochemical markers of blood glutathione between DM and PAC groups (p > .05). Quantitative comparisons of peripheral nerves by intraepidermal nerve fiber density (IENFD) analysis indicated that the DM and PAC groups were similar (6.18 ± 1.03 vs. 5.01 ± 2.57). IENFD was significantly improved after ALA and DA-9801 treatment in diabetic animals (7.6 ± 1.28, 7.7 ± 1.28, respectively, p < .05) but did not reach significance in the PAC-treated groups (6.05 ± 1.76, 5.66 ± 1.26, respectively, p > .05). Sciatic nerves were less damaged in the PAC-treated groups compared with the DM groups with respect to axonal diameter and area (8.60 ± 1.14 µm vs. 6.66 ± 1.07 µm, and 59.04 ± 15.16 µm2 vs. 35.71 ± 11.2 µm2, respectively, p < .05). Based on these results, the neuropathic manifestation and therapeutic responses of DPN may be different from other peripheral neuropathies. Therefore, specific pathogenic consideration according to peripheral neuropathy classification in addition to common treatments needs to be developed for management strategies of peripheral neuropathies.

Common Salivary Protein 1 in Serum of Diabetes Patients.

BACKGROUND: Recently, the human common salivary protein 1 (CSP1) was identified as an ortholog of the Demilune cell and parotid protein of mouse. However, its function remains to be determined. Here, we show that the serum CSP1 concentration of diabetes mellitus (DM) patients is much higher than that of healthy controls. METHODS: Recombinant human CSP1 was expressed as a Glutathione-S-transferase (GST)-tagged protein, and the purified fusion protein was used as an immunogen to generate monoclonal antibody (mAb) to CSP1. The produced mAb was tested as a probe in Western blotting of human saliva and in immunohistochemistry of various human tissues. The serum CSP1 levels of 31 DM patients and 38 normal adults were quantified by a house-fabricated CSP1 sandwich enzyme-linked immunosorbent assay (ELISA) system. RESULTS: Immunoblot analysis by mAb-hCSP1#4 showed that CSP1 in human saliva exists in a 27 kDa glycosylated form. Among the various human tissues tested, the salivary gland was the only tissue stained with mAb-hCSP1#4 by immunohistochemistry. Quantification of serum CSP1 concentration by CSP1 ELISA showed that the median values (25th-75th percentile) of DM patients and healthy adults were 22.2 (15.8-28.2) and 3.2 (0-11.4), respectively. Student's t-test results indicated that there was a statistically significant difference between the two groups (P < 0.01). CONCLUSION: The significant difference between the CSP1 levels of the two groups indicated that CSP1 would be a potential biomarker for detection or screening of DM patients.

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.

Dyslipidemia Fact Sheet in South Korea, 2022.

BACKGRUOUND: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. METHODS: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. RESULTS: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia-more than one out of three conditions (low-density lipoprotein cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein cholesterol [HDL-C] [men and women] <40 mg/dL)-was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-HDL-cholesterolemia in women changed from <40 to <50 mg/dL. CONCLUSION: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Dyslipidemia Fact Sheet in South Korea, 2022.

Objective: This study aimed to investigate the prevalence and status of dyslipidemia management among South Korean adults, as performed by the Korean Society of Lipid and Atherosclerosis under the name Dyslipidemia Fact Sheet 2022. Methods: We analyzed the lipid profiles, age-standardized and crude prevalence, management status of hypercholesterolemia and dyslipidemia, and health behaviors among Korean adults aged ≥20 years, using the Korea National Health and Nutrition Examination Survey data between 2007 and 2020. Results: In South Korea, the crude prevalence of hypercholesterolemia (total cholesterol ≥240 mg/dL or use of a lipid-lowering drug) in 2020 was 24%, and the age-standardized prevalence of hypercholesterolemia more than doubled from 2007 to 2020. The crude treatment rate was 55.2%, and the control rate was 47.7%. The crude prevalence of dyslipidemia (more than one out of three conditions [low-density lipoprotein-cholesterol ≥160 or the use of a lipid-lowering drug, triglycerides ≥200, or high-density lipoprotein-cholesterol (men and women) <40 mg/dL]) was 40.2% between 2016 and 2020. However, it increased to 48.2% when the definition of hypo-high-density lipoprotein-cholesterolemia in women changed from <40 to <50 mg/dL. Conclusion: Although the prevalence of hypercholesterolemia and dyslipidemia has steadily increased in South Korea, the treatment rate remains low. Therefore, continuous efforts are needed to manage dyslipidemia through cooperation between the national healthcare system, patients, and healthcare providers.

Public Awareness of Dyslipidemia Among the Korean Population: A Survey Study.

Objective: We aimed to assess the level of public awareness regarding dyslipidemia and its management among the Korean population. Methods: We conducted a web- or mobile-based survey study targeting the general population, using various recruitment methods, between July 25, 2022 and August 26, 2022. The questionnaire consisted of 12 questions designed to collect demographic information and evaluate participants' awareness and knowledge about dyslipidemia. Results: In total, 2,882 participants who completed the survey were included in the analysis. Among the participants, a substantial majority (89.1%) were familiar with the concepts of "good cholesterol" and "bad cholesterol," while a comparatively lower percentage (just 46.7%) were acquainted with the term "dyslipidemia." Noticeable variations in understanding were observed when examining specific aspects of dyslipidemia management, including diet, exercise, and pharmacotherapy. Conclusion: The results of this survey underscore the significance of enhancing public awareness about dyslipidemia within the context of health literacy, demonstrating the necessity for a more comprehensive approach that includes education and policymaking to effectively manage dyslipidemia.

The effects of designed angiopoietin-1 variant on lipid droplet diameter, vascular endothelial cell density and metabolic parameters in diabetic db/db mice.

Metabolic syndrome consists of metabolic abnormality with central obesity, hypertriglyceridemia, insulin resistance and hypertension. Adipose tissue has been known as a primary site of insulin resistance and its adipocyte size may be correlated with the degree of insulin resistance. A designed angiopoietin-1, COMP-Angiopoietin-1 (COMP-Ang1), mitigated high-fat diet-induced insulin resistance in skeletal muscle. In this study, we examined effects of COMP-Ang1 on adipocyte droplet size, vascular endothelial cell density in adipose tissue and metabolic parameters in db/db mice by administering COMP-Ang1 or LacZ (as a control) adenovirus. Administration of COMP-Ang1 decreased fat droplet diameter in epididymal and abdominal visceral adipocyte and visceral fat content in db/db mice. The density of vascular endothelial cell in adipose tissue was increased in db/db mice after treatment with COMP-Ang1. Serum resistin and tumor necrosis factor-α level was lower after treatment with COMP-Ang1 in db/db mice. COMP-Ang1 caused a restoration of fasting glycemic control in db/db mice and decreased serum insulin level and insulin resistance measured by HOMA index. These findings indicate that COMP-Ang1 regulates adipocyte fat droplet diameter, vascular endothelial cell density and metabolic parameters in db/db mice.

Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats.

Dipeptidyl peptidase (DPP) IV inhibitors are probably beneficial for preventing diabetic complication and modulating glucagon-like peptide-1 receptor (GLP-1R) expression. The aim of this study was to determine whether the DPP IV inhibitor LAF237 (vildagliptin) has renoprotective qualities in streptozotocin-induced diabetic rats. Diabetic and nondiabetic rats were treated with an oral dose of 4 or 8 mg/kg/day LAF237 or placebo for 24 weeks, and renal injury was observed by light and electron microscopy. We also assessed DPP IV activity, active GLP-1 level, cAMP and 8-hydroxy-deoxyguanosine excretion, and GLP-1R, cleaved caspase 3, and transforming growth factor-ß1 (TGF-ß1) expression. LAF237 significantly decreased proteinuria, albuminuria, and urinary albumin/creatinine ratio, improved creatinine clearance, and dose-dependently inhibited interstitial expansion, glomerulosclerosis, and the thickening of the glomerular basement membrane in diabetic rats. It is noteworthy that LAF237 markedly down-regulated DPP IV activity and increased active GLP-1 levels, which probably prevented oxidative DNA damage and renal cell apoptosis by activating the GLP-1R and modulating cAMP. Renoprotection was also associated with a reduction in TGF-ß1 overexpression. Our study suggests that DPP IV inhibitors may ameliorate diabetic nephropathy as well as reduce the overproduction of TGF-ß1. The observed renoprotection is probably attributable to inhibition of DPP IV activity, mimicking of incretin action, and activation of the GLP-1R.

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.

Primary aldosteronism presenting as embolic myocardial infarction.

INTRODUCTION: Primary aldosteronism is now recognized as the most common cause of secondary hypertension. Increasing evidence has demonstrated increased cardiovascular events in primary aldosteronism patients. Heart failure and atrial fibrillation are the most common cardiovascular complications occurring in these patients, and a few cases of coronary artery disease have been reported. Herein, we report a rare case of primary aldosteronism in a patient who presented with myocardial infarction associated with coronary embolism. CASE REPORT: A 52-year-old woman was admitted to our hospital because of chest pain. ST-segment elevation was observed on an electrocardiogram. Although no significant stenosis was observed, embolization of the far distal left anterior descending artery was noticed on angiography. Blood test results revealed hypokalemia and increased aldosterone-renin ratio. Abdominal computed tomography revealed an adenoma in the left adrenal gland. After adrenalectomy, the serum potassium level normalized, and blood pressure was well controlled. CONCLUSION: Primary aldosteronism must be considered in patients who have had various cardiovascular diseases, including embolisms and situations in which the discrimination of secondary hypertension is necessary.

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.

Mainly adrenal gland involving NK/T-cell nasal type lymphoma diagnosed with delay due to mimicking adrenal hemorrhage.

A 29-yr-old man, presented with abdominal pain and fever, had an initial computed tomography (CT) scan revealing low attenuation of both adrenal glands. The initial concern was for tuberculous adrenalitis or autoimmune adrenalitis combined with adrenal hemorrhage. The patient started empirical anti-tuberculous medication, but there was no improvement. Enlargement of cervical lymph nodes were developed after that and excisional biopsy of cervical lymph nodes was performed. Pathological finding of excised lymph nodes was compatible to NK/T-cell lymphoma. The patient died due to the progression of the disease even after undergoing therapeutic trials including chemotherapy. Lymphoma mainly involving adrenal gland in the early stage of the disease is rare and the vast majority of cases that have been reported were of B-cell origin. From this case it is suggested that extra-nodal NK/T-cell lymphoma should be considered as a cause of bilateral adrenal masses although it is rare.

Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals.

The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but failing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinated fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.

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.

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.