Medial Arterial Calcification and the Risk of Amputation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease.

We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b-5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.

Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study.

BACKGROUND: The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. METHODS: This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004-2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012-2016). RESULTS: The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04-14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96-15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42-11.1, p < 0.01). CONCLUSION: Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

Efficacy and safety of lobeglitazone versus sitagliptin as an add-on to metformin in patients with type 2 diabetes with two or more components of metabolic syndrome over 24 weeks.

We aimed to evaluate the efficacy and safety profile of lobeglitazone compared with sitagliptin as an add-on to metformin in patients with type 2 diabetes as well as other components of metabolic syndrome. Patients inadequately controlled by metformin were randomly assigned to lobeglitazone (0.5 mg, n = 121) or sitagliptin (100 mg, n = 126) for 24 weeks. The mean changes in HbA1c of the lobeglitazone and sitagliptin groups were -0.79% and -0.86%, respectively; the between-group difference was 0.08% (95% confidence interval, -0.14% to 0.30%), showing non-inferiority. The proportion of patients having two or more factors of other metabolic syndrome components decreased to a greater extent in the lobeglitazone group than in the sitagliptin group (-11.9% vs. -4.8%; P < .0174). Favourable changes in the lipid metabolism were also observed with lobeglitazone, which had a similar safety profile to sitagliptin. Lobeglitazone was comparable with sitagliptin as an add-on to metformin in terms of efficacy and safety.

Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study (TROICA study).

AIMS: To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. RESULTS: The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group. CONCLUSIONS: Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. APPROACH AND RESULTS: This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. CONCLUSIONS: Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.

CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic beta-cells.

Diverse mechanisms are involved in the pathogenesis of ß-cell failure in type 2 diabetes. Of them, the accumulation of ceramide, a bioactive lipid metabolite, is suggested to play a major role in inflammatory and stress responses that induce diabetes. However, the downstream inflammatory target of ceramide has not been defined. Using rat islets and the INS-1 ß-cell line, we hypothesized that activation of the redox sensitive protein TXNIP is involved in ceramide-induced ß-cell dysfunction. Incubation of INS-1 cells and primary islets with C2-ceramide (N-acetyl-sphingosine) downregulated insulin and PDX-1 expression and increased ß-cell apoptosis. Ceramide treatment induced a time dependent increase in TXNIP gene expression accompanied by activation of nuclear factor (NF)-κB and reduced mitochondrial thioredoxin (TRX) activity. Pretreatment with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked ceramide-induced up-regulation of TXNIP expression and activity of NF-κB. Blockade of NF-κB nuclear translocation by the peptide SN50 prevented ceramide-mediated TXNIP induction. Furthermore, SSO also attenuated ceramide-induced early loss of insulin signaling and apoptosis. Collectively, our results unveil a novel role of CD36 in early molecular events leading to NF-κB activation and TXNIP expression. These data suggest that CD36 dependent NF-κB-TXNIP signaling contributes to the ceramide-induced pathogenesis of pancreatic ß-cell dysfunction and failure.

The Glucotoxicity Protecting Effect of Ezetimibe in Pancreatic Beta Cells via Inhibition of CD36.

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to determine whether this effect is related to change of CD36 expression. mRNA expression of insulin and CD36, intracellular peroxide level and glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose (30 mM) condition in INS-1 cells and primary rat islet cells were compared. Changes of the aforementioned factors with treatment with ezetimibe (20 µM) under normal or high glucose condition were also assessed. mRNA expression of insulin was decreased with high glucose, which was reversed by ezetimibe in both INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three-day treatment with high glucose resulted in an increase in intracellular peroxide level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake following exposure to high glucose conditions for three days was significantly elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent glucotoxicity in pancreatic ß-cells through a decrease in fatty acid influx via inhibition of CD36.

Comparison of acarbose and voglibose in diabetes patients who are inadequately controlled with basal insulin treatment: randomized, parallel, open-label, active-controlled study.

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% ± 0.71% to 7.71% ± 0.93%) and voglibose groups (from 8.38% ± 0.73% to 7.68% ± 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 ± 69.38 to 176.80 ± 46.63 mg/dL) compared with the voglibose group (from 224.18 ± 70.07 to 193.01 ± 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528).

Waste to Energy: Steam explosion-based torrefaction process to produce solid biofuel for power generation utilizing various waste biomasses.

Currently, humankind is facing a serious environmental and climate crisis, which has accelerated the research on producing bioenergy from waste biomass as a carbon-neutral feedstock. In this study, the aim was to develop an upcycling strategy for waste biomass to solid-type biofuel conversion for power generation. Various types of waste biomass (i.e., waste wood after lumbering, sawdust-type mushroom waste wood, kudzu vine, and empty fruit bunches from palm) were used as sustainable feedstocks for steam explosion-based torrefaction. The reaction conditions were optimized for each waste biomass by controlling the severity index (Ro); the higher heating value increased proportional to the Ro increase. Additionally, component analysis revealed that steam explosion torrefaction mainly degraded hemicellulose, and most of the torrefied waste biomass met the Bio-Solid Refuse Fuel quality standard. The results provide not only a viable waste-to-energy strategy but also insights to address global climate change.

Predictive factors of lymph node metastasis in papillary thyroid cancer.

This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.

Inhibition of fatty acid translocase cluster determinant 36 (CD36), stimulated by hyperglycemia, prevents glucotoxicity in INS-1 cells.

The purpose of the present study was to determine whether exposure of pancreatic islets to glucotoxic conditions changes fatty acid translocase cluster determinant 36 (CD36) and examine the role of CD36 on the induction of glucotoxicity. We measured the changes of CD36 and insulin secretion in high glucose (30 mM) exposed INS-1 cells and CD36 suppressed INS-1 cells by transfection of CD36 siRNA. The intracellular peroxide level of INS-1 cells increased in the high glucose media compared to normal glucose (5.6mM) media. The mRNA levels of insulin and PDX-1, as well as glucose stimulated insulin secretion (GSIS) were decreased in INS-1 cells exposed to high glucose media compared to normal glucose media, while CD36 and palmitate uptake were significantly elevated with exposure to high glucose media for 12h. The inhibition of CD36 reversed the decreased GSIS and intracellular peroxide level in INS-1 cells. These results suggest that high glucose may exacerbate glucotoxicity via increasing fatty acid influx by elevation of CD36 expression, and that CD36 may be a possible target molecule for preventing glucotoxicity in pancreatic beta-cells.

Ceramide 1-phosphate induces neointimal formation via cell proliferation and cell cycle progression upstream of ERK1/2 in vascular smooth muscle cells.

Ceramide 1-phosphate (C1P) is a novel bioactive sphingolipid formed by ceramide kinase (CERK)-catalyzed phosphorylation of ceramide. It has been implicated in the regulation of such vital pathophysiological functions as phagocytosis and inflammation, but there have been no reports ascribing a biological function to CERK in vascular disorders. Here the potential role of CERK/C1P in neointimal formation was investigated using rat aortic vascular smooth muscle cells (VSMCs) in primary culture and a rat carotid injury model. Exogenous C8-C1P stimulated cell proliferation, DNA synthesis, and cell cycle progression of rat aortic VSMCs in primary culture. In addition, wild-type CERK-transfected rat aortic VSMCs induced a marked increase in rat aortic VSMC proliferation and [(3)H]-thymidine incorporation when compared to empty vector transfectant. C8-C1P markedly activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) within 5min, and the activation could be prevented by U0126, a MEK inhibitor. Also, K1, a CERK inhibitor, decreased the ERK1/2 phosphorylation and cell proliferation on platelet-derived growth factor (PDGF)-stimulated rat aortic VSMCs. CERK expression and C1P levels were found to be potently increased during neointimal formation using a rat carotid injury model. However, ceramide levels decreased during the neointimal formation process. These findings suggest that C1P can induce neointimal formation via cell proliferation through the regulation of the ERK1/2 protein in rat aortic VSMCs and that CERK/C1P may regulate VSMC proliferation as an important pathogenic marker in the development of cardiovascular disorders.

Usefulness of glycated hemoglobin as diagnostic criteria for metabolic syndrome.

The metabolic syndrome (MetS) is the clustering of cardiovascular risk factors and known as a powerful predictor of diabetes and cardiovascular disease. Glycated hemoglobin (HbA1c) is used as one of the diagnostic criteria for diabetes and category of increased risk for diabetes. We examined the usefulness of HbA1c as a diagnostic tool for MetS and to determine the cut-off value of HbA1c as a criterion for MetS, in non-diabetic Korean subjects. We analyzed 7,307 participants (male: 4,181, 57%) in a medical check-up program, and applied the newly recommended guidelines of the International Diabetes Federation for diagnosis of MetS. The mean HbA1c was 5.54% in all subjects and showed no significant difference between genders. Using receiver-operating characteristic curve, HbA1c value corresponding to the fasting plasma glucose value of 100 mg/dL was 5.65% (sensitivity 52.3%, specificity 76.7%). The prevalence of MetS was 8.5% according to the IDF guideline and 10.9% according to HbA1c value of 5.7%, showing 69.5% agreement rate. The detection rate of MetS increased to 25.7% using the HbA1c criterion of 5.7% instead of fasting hyperglycemia. This study suggests that HbA1c might be used as a diagnostic criterion for MetS and the appropriate cut-off value of HbA1c may be 5.65% in this Korean population.

Association between nutrient intake and obesity in type 2 diabetic patients from the Korean National Diabetes Program: a cross-sectional study.

The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (P(trend) = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (P(trend) = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (P(trend) < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198).

Long-term effects of the changes in hepatic steatosis status on the risk of incident type 2 diabetes mellitus: A 15-year community-based prospective cohort study.

AIMS: We investigated the long-term effect of changes in hepatic steatosis on the risk of developing T2DM. METHODS: We evaluated 3510 participants from the 2001-2016 Korean Genome and Epidemiology Study. Those with significant alcohol consumption or T2DM during 2001-2004 were excluded. Steatosis was defined as non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS) of over -0.64, and baseline values were assessed between 2001 and 2002. Differences in NAFLD-LFS (ΔLFS) and changes in steatosis status (no, intermittent [resolved or incident], and persistent steatosis) were assessed between 2003 and 2004. Changes in the risk of diabetes status were observed until 2016. RESULTS: Over 52,650 person-years of follow-up, T2DM developed in 296 participants (8.4%). The incidence of diabetes in those with no steatosis, intermittent steatosis, and persistent steatosis during follow-up increased by 5.1%, 14.1%, and 27.1% respectively. Multivariate-adjusted analysis revealed that the risk was higher in those with persistent steatosis than those with no steatosis and intermittent steatosis. Baseline NAFLD-LFS and ΔLFS was associated with increased risk of incident T2DM. CONCLUSIONS: Initial severity as well as aggravation of steatosis is an independent predictor of incident T2DM. Strategies aimed at reducing liver fat may prevent future development of diabetes among patients with NAFLD.

Early glycaemic variability increases 28-day mortality and prolongs intensive care unit stay in critically ill patients with pneumonia.

OBJECTIVE: This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia. PATIENTS AND METHODS: This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (>14 days) were also assessed. RESULTS: The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (n = 89) and was not different according to the presence of diabetes (DM vs. non-DM) or HbA1c levels (≥7.5 vs. <7.5%; both p > .05). However, the mortality rate was significantly higher in patients with high GV (CV ≥ 36%) than in those with low GV (CV < 36%; 37.5 vs. 25.4%, p = .028). The risk of mortality in patients with high GV was prominent in the subgroups with DM or low HbA1c levels. Among the surviving patients (n = 193), 44 remained in the ICU for more than 14 days. Compared to low GV, high GV was associated with a higher rate of prolonged ICU stay, although not statistically significant (27.8 vs. 18.5%, p = .171). After adjusting for the severity of illness and treatment strategy, CV was an independent risk factor for 28-day mortality (hazard ratio [HR], 1.01, p = .04) and prolonged ICU stay (odds ratio, 1.02; p = .04). CONCLUSIONS: High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (<7.5%) should be more carefully treated to reduce mortality.

Idesolide, an isolate of Idesia polycarpa, inhibits apoptosis through induction of intracellular heat shock protein 70 in C2C12 muscle cells.

Muscle disorders, such as muscular dystrophy, are associated with an increase in oxidative stress. Proposed treatments for muscular dystrophy, some in clinical trials, include gene therapy and muscle cell transplantation. In this study, we investigated the effects of idesolide, isolated from the fruits of Idesia polycarpa, on changes that occur in muscle disuse atrophy. We noted protective effects on oxidative stress response and HSP70 regulation. Pre-treatment with idesolide for 24 h maintained cell viability and decreased apoptosis in H(2)O(2)-treated C(2)C(12) muscle cells. The idesolide pretreatment also increased intracellular HSP70 protein. Our results suggest that idesolide inhibits cell death through induction of HSP70 in C(2)C(12) muscle cells. This work is the first to report that idesolide can regulate the decrease in HSP70 that occurs during skeletal muscle atrophy.

Risk factors affecting amputation in diabetic foot.

BACKGROUND: A diabetic foot is the most common cause of non-traumatic lower extremity amputations (LEA). The study seeks to assess the risk factors of amputation in patients with diabetic foot ulcers (DFU). METHODS: The study was conducted on 351 patients with DFUs from January 2010 to December 2018. Their demographic characteristics, disease history, laboratory data, ankle-brachial index, Wagner classification, osteomyelitis, sarcopenia index, and ulcer sizes were considered as variables to predict outcome. A chi-square test and multivariate logistic regression analysis were performed to test the relationship of the data gathered. Additionally, the subjects were divided into two groups based on their amputation surgery. RESULTS: Out of the 351 subjects, 170 required LEA. The mean age of the subjects was 61 years and the mean duration of diabetes was 15 years; there was no significant difference between the two groups in terms of these averages. Osteomyelitis (hazard ratio [HR], 6.164; 95% confidence interval [CI], 3.561-10.671), lesion on percutaneous transluminal angioplasty (HR, 2.494; 95% CI, 1.087-5.721), estimated glomerular filtration rate (eGFR; HR, 0.99; 95% CI, 0.981-0.999), ulcer size (HR, 1.247; 95% CI, 1.107-1.405), and forefoot ulcer location (HR, 2.475; 95% CI, 0.224-0.73) were associated with risk of amputation. CONCLUSION: Osteomyelitis, peripheral artery disease, chronic kidney disease, ulcer size, and forefoot ulcer location were risk factors for amputation in diabetic foot patients. Further investigation would contribute to the establishment of a diabetic foot risk stratification system for Koreans, allowing for optimal individualized treatment.

The sex-specific effects of blood lead, mercury, and cadmium levels on hepatic steatosis and fibrosis: Korean nationwide cross-sectional study.

AIM: The potential effects of heavy metals on non-alcoholic fatty liver disease (NAFLD) remain unknown. We investigated the sex-specific relationships of blood lead (BPb), mercury (BHg), and cadmium (BCd) levels with hepatic steatosis (HS) and fibrosis (HF). METHOD: We included 4420 participants from the 2016-2017 Korea National Health and Nutrition Examination Survey. High-risk alcoholics and patients with chronic hepatitis B or C infections or liver cirrhosis were excluded. We calculated the hepatic steatosis index (HSI) and fibrosis-4 index (FIB-4) values; we defined the presence of HS and HF as an HSI ≥ 36 and FIB-4 score >2.67, respectively. We adjusted for age, smoking and alcohol consumption statuses, hypertension, obesity, diabetes, hypertriglyceridemia, and BPb, BHg, and BCd levels. RESULT: In males (n = 1860), the HSI was correlated negatively with the BPb level and positively with the BHg level (both p < 0.01). The FIB-4 score was correlated positively with the BPb and BCd levels (both p < 0.01). In females (n = 2560), the HSI and FIB-4 score were correlated positively with the BPb, BHg, and BCd levels (all p < 0.01). After adjustments, the BHg level increased the risk of HS in both males (OR = 1.065, p = 0.003) and females (OR = 1.061, p = 0.048), and the BCd level increased the risk of HF in females (OR = 1.668, p = 0.012). CONCLUSION: Blood heavy metal levels were generally correlated positively with the HSI and FIB4 score, more so in females than males. The BHg level was associated with HS in males and females, and the BCd level was associated with HF in females. Further studies on NAFLD progression according to heavy metal status and sex are warranted.

Low alanine aminotransferase levels predict low muscle strength in older patients with diabetes: A nationwide cross-sectional study in Korea.

AIM: Low alanine aminotransferase (ALT) level is associated with frailty in the older adult population. We investigated the usefulness of ALT in predicting low muscle strength among older patients with diabetes. METHODS: We included 550 men aged ≥50 years and 525 postmenopausal women. All participants had diabetes, and data were based on the 2014-2016 Korea National Health and Nutrition Examination Survey. Participants with ALT levels confounded by hepatic causes or who had a cerebrovascular accident were excluded. The accompanying metabolic disorders and the associated parameters were evaluated. Low muscle strength was defined as handgrip strength below the Korean-specific cut-off value. RESULTS: In men and women, when ALT level was divided into quartiles (Q1-Q4), a positive correlation between ALT and body mass index, triglycerides, fasting plasma glucose, glycated hemoglobin levels and handgrip strength was observed, whereas a negative correlation was observed with age and duration of diabetes (P < 0.05, all). After adjusting for age, sex, protein intake, aerobic exercise, body mass index, duration of diabetes, glycated hemoglobin and triglycerides, the lower ALT quartiles ([Q1 and Q2) showed a higher risk for low muscle strength compared with Q4 (OR 2.123 and 2.437; P = 0.060 and 0.029). The cut-off ALT level for low muscle strength was 18.5 IU/L. CONCLUSION: Older patients with diabetes with ALT levels below low-to-normal should not be considered metabolically healthy. Clinicians should pay special attention to the risk of low muscle strength in individuals with ALT levels of ≤18.5 IU/L, independent of any associated metabolic disorders. Geriatr Gerontol Int 2020; 20: 271-276.