Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.

Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Impaired fasting glucose levels in overweight or obese subjects for screening of type 2 diabetes in Korea.

BACKGROUND/AIMS: We examined the concordance rate among fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hr PG), and hemoglobin A1c (HbA1c) in the diagnosis of diabetes in a population with a high-risk for type 2 diabetes mellitus (T2DM) in Korea. METHODS: Among the participants from the Korean Diabetes Prevention Study, individuals with FPG ≥ 100 mg/dL, body mass index (BMI) ≥ 23.0 kg/m2, and no previous history of T2DM were consecutively enrolled after a 75 g glucose tolerance test. We analyzed the differences in the clinical characteristics in subjects with stage 1 (FPG, 100 to 109 mg/dL) and stage 2 (FPG, 110 to 125 mg/dL) impaired fasting glucose (IFG). RESULTS: Of 1,637 participants, 27.2% had T2DM and 59.3% had IFG and/or impaired glucose tolerance (IGT). The mean age was 55.0 ± 8.1 years and the mean BMI was 26.3 ± 2.7 kg/m2. Based on FPG criteria, 515 (31.4%) and 352 (21.5%) subjects were classified as having stage 1 and stage 2 IFG, respectively. The 19.0% of stage 1 and 43.5% of stage 2 subjects showed 2hr PG levels in the diabetic range. Even for those in the normal FPG range, 63 (9.5%) participants showed a 2hr PG level of ≥ 200 mg/dL. Of 446 subjects with newly-diagnosed diabetes, 340 (76.2%) showed FPG levels < 126 mg/dL. CONCLUSION: The oral glucose tolerance test should be actively considered for Korean adults who are overweight or obese with the IFG range (FPG, 100 to 125 mg/ dL) to allow for early detection of diabetes and prompt intervention.

GENetic characteristics and REsponse to lipid-lowering therapy in familial hypercholesterolemia: GENRE-FH study.

Among the 146 patients enrolled in the Korean FH registry, 83 patients who had undergone appropriate LLT escalation and were followed-up for ≥ 6 months were analyzed for pathogenic variants (PVs). The achieved percentage of expected low-density lipoprotein-cholesterol (LDL-C) reduction (primary variable) and achievement rates of LDL-C < 70 mg/dL were assessed. The correlations between the treatment response and the characteristics of PVs, and the weighted 4 SNP-based score were evaluated. The primary variables were significantly lower in the PV-positive patients than in the PV-negative patients (p = 0.007). However, the type of PV did not significantly correlate with the primary variable. The achievement rates of LDL-C < 70 mg/dL was very low, regardless of the PV characteristics. Patients with a higher 4-SNP score showed a lower primary variable (R2 = 0.045, p = 0.048). Among evolocumab users, PV-negative patients or those with only defective PVs revealed higher primary variable, whereas patients with at least one null PV showed lower primary variables. The adjusted response of patients with FH to LLT showed significant associations with PV positivity and 4-SNP score. These results may be helpful in managing FH patients with diverse genetic backgrounds.

Efficacy and Tolerability of Pitavastatin Versus Pitavastatin/Fenofibrate in High-risk Korean Patients with Mixed Dyslipidemia: A Multicenter, Randomized, Double-blinded, Parallel, Therapeutic Confirmatory Clinical Trial.

PURPOSE: Dyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD. METHODS: This multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150-500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non-HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment. FINDINGS: The difference in the mean percentage change in non-HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was -12.45% (95% CI, -17.18 to -7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non-HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. IMPLICATIONS: In these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non-HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.

Optimal fasting plasma glucose and haemoglobin A1c levels for screening of prediabetes and diabetes according to 2-hour plasma glucose in a high-risk population: The Korean Diabetes Prevention Study.

BACKGROUND: The primary aim of this study was to assess the utility of fasting plasma glucose (FPG) and HbA1c to identify diabetes by the 2-hour plasma glucose (PG) criterion in the Korean population at high risk for diabetes. METHODS: A total of 1646 participants with a body mass index of ≥23 kg/m2 without having a history of diabetes were recruited in this study. The cut-off values of FPG and HbA1c for detecting diabetes were identified using the Youden index using receiver operating characteristic (ROC) analysis. The gold standard for diabetes prediction was defined by the 2-hour PG level of ≥200 mg/dL. RESULTS: The participants comprised 54.0% women, and the mean age of all participants was 55.0 ± 8.1 years. At baseline, FPG was 104.1 ± 14.2 mg/dL, the 2-hour PG value was 162.9 ± 55.3 mg/dL, and HbA1c was 5.9% ± 0.5%. Four hundred and forty-six subjects (27.1%) were diagnosed with diabetes and 976 subjects (59.3%) were determined to be at prediabetes. The area under the ROC curve (AUC) of FPG and HbA1c for diabetes were 0.776 and 0.802, while the AUC of FPG and HbA1c for prediabetes were 0.515 and 0.477. The optimal cut-off value for diagnosing diabetes of FPG and HbA1c were 104.5 mg/dL (sensitivity 75.8%, specificity 67.5%) and 5.9% (sensitivity 80.6%, specificity 63.8%), respectively. CONCLUSIONS: FPG of 104.5 mg/dL and HbA1c value of 5.9% (41 mmol/mol) can be used as an optimal screening value for diabetes by 2-hour PG criterion in the Korean population at high risk for diabetes.

Incidence of Diabetes Mellitus in Male Moderate Alcohol Drinkers: A Community-Based Prospective Cohort Study.

BACKGROUND/AIM: Although alcohol consumption is known to affect the incidence of diabetes mellitus (DM), reports on the effects of moderate alcohol consumption on DM incidence have been inconsistent. This community-based prospective cohort study was performed to investigate the incidence of DM in male Korean moderate alcohol drinkers. METHODS: The Ansan and Ansung cohort was used for the analysis. The study population included a total of 3,492 men with no history of DM. The subjects were classified as mild (1-14 g/d), moderate (15-29 g/d), and heavy (≥30 g/d) drinkers based on their amount of alcohol consumption. The incidence rates of DM in the three groups were compared and analyzed over a 10 year follow-up period. RESULTS: The hazard ratios (HRs) for DM incidence were 25.12 (95% confidence interval [CI], 21.73-28.90) per 1,000 person years (PY) in mild drinkers, 31.13 (26.11-36.83) per 1,000 PY in moderate drinkers, and 31.68 (26.81-37.18) per 1,000 PY in heavy drinkers (p for trend, p = 0.043). Multivariate regression analysis showed that the HRs (95% CI) for DM were 1.25 (0.97-1.61, p = 0.086) in moderate drinkers and 1.30 (1.01-1.68, p = 0.045) in heavy drinkers compared to mild drinkers. The changes in pancreatic insulin secretion were more remarkable than those in insulin resistance in all three groups. CONCLUSIONS: The incidence of DM in male Korean moderate drinkers did not increase significantly over the observation period. However, the incidence of DM tended to increase with increasing alcohol consumption. Pancreatic insulin secretion may play a more important role than insulin resistance in the relationship between alcohol and incidence of DM.

Genome-wide association study identifies new susceptibility loci for diabetic nephropathy in Korean patients with type 2 diabetes mellitus.

Genetic factors are considered to be important in the pathogenesis of diabetic nephropathy (DN). Despite several genome-wide association studies (GWASs) demonstrating that specific polymorphisms of candidate genes were associated with DN, there were some limitations in previous studies. We conducted a GWAS using customized DNA chips to identify novel susceptibility loci for DN in Korean. We analyzed a total of 414 DN cases and 474 normoalbuminuric diabetic hyper-controls across two stages using customized DNA chips containing 98 667 single nucleotide polymorphisms (SNPs). We explored the associations between SNPs and DN in samples from 87 DN cases, mostly confirmed by renal biopsy, and 104 diabetic hyper-controls, and replicated these associations in independent cohort samples with 327 DN cases and 370 diabetic hyper-controls. The top significant SNPs from the discovery samples were selected for replication in the independent cohort. rs3765156 in PIK3C2B was significantly associated with DN in the replication cohort after multiple test. The SNPs identified in our study provide new insights into the pathogenesis of DN in the Korean population. Additional studies are needed to determine biological effects and clinical utility of our findings.

Analysis of diabetes quality assessment findings and future directions for the appropriate management of diabetes in Korea.

BACKGROUND/AIMS: Due to recent increases in the disease burden of diabetes mellitus, the Health Insurance Review and Assessment Service (HIRA) of Korea implemented a quality assessment of the treatment of diabetes to improve patient care. The present study was conducted to identify any changes after the implementation of the diabetes quality assessment (DQA). METHODS: The present study evaluated eight quality assessment indicators that were proposed by the HIRA in all patients with diabetes who visited a university hospital in Korea between 2009 and 2014. The indicators were statistically compared according to the characteristics of the subjects. RESULTS: There were several significant differences in the indicators among the subjects according to their demographic characteristics. Female patients had a higher continuity of treatment (COT) than that of male patients, and the insulin-treated group had a higher COT than that of the non-treated group, as well as a higher rate of undergoing the diabetes complication tests (DCTs). Patients between 40 and 80 years of age had the highest COT, while patients under 40 years of age had the lowest COT but the highest rate of taking the DCTs. Patients receiving treatment from an endocrinologist exhibited higher numbers of DCTs performed but displayed lower proportions for the prescription indicators. CONCLUSION: The present analysis of the DQA findings revealed that endocrinologists combine prevention and management of diabetes complications with measures for glycemic control. Thus, the effective management of diabetes likely entails systematic joint treatment regimens that involve an endocrinologist.

Importance of family history of diabetes in computing a diabetes risk score in Korean prediabetic population.

Prediabetic subjects represent a vulnerable population, requiring special care to reduce the risk of diabetes onset. We developed and validated a diabetes risk score for prediabetic subjects using the Korea National Diabetes Program (KNDP) cohort. Subjects included in the multicenter and prospective cohort (n = 1162) had high diabetes risk at baseline (2005) and were followed until 2012. Survival analysis was performed to analyze the prospective cohort over time, and the bootstrap method was used to validate our model. We confirmed our findings in an external cohort. A diabetes risk score was calculated and the cut-off defined using a receiver operating characteristic curve. Age, body mass index, total cholesterol, and family history of diabetes were associated with diabetes. The model performed well after correction for optimism (Cadj = 0.735). A risk score was defined with a cut-off of ≥5 that maximized sensitivity (72%) and specificity (62%), with an area under the curve of 0.73. Prediabetic subjects with a family history of diabetes had a higher probability of diabetes (risk score = 5) irrespective of other variables; this result was confirmed in the external cohort. Hence, prediabetic subjects with a family history of diabetes have a higher probability of developing diabetes, regardless of other clinical factors.

Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy.

INTRODUCTION: Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication. OBJECTIVES: We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration ≥ 15 years. METHODS: A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics. RESULTS: For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC = 0.739) and the ratio (AUC = 0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses. CONCLUSION: Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ≥30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients < 65 years of age, patients with a T2DM duration < 5 years, nonobese patients, nonsmokers, and good glycemic control group.This large-scale, prospective, multicenter cohort study demonstrated an association between metformin use and reduced cancer risk in patients with T2DM.

A Nutrition Intervention Focused on Weight Management Through Lifestyle Improvements in Prediabetic Subjects.

We reported the cases in order to evaluate the effects of individualized nutrition interventions for enhancing self-management abilities of prediabetic subjects. We conducted four nutrition interventions for weight control in two subjects with high-risk of type 2 diabetes. The first subject was a 53-year-old housewife, and the second subject was a 46-year-old male office worker. The subjects visited the medical center 4 times during the study period, and the lifestyle interventions were advised by a clinical team comprised physicians, clinical dietitians, and nurses. In particular, nutrition intervention to achieve weight loss focused on enhancing motivation and problem-solving skills to improve self-management ability. As a result, both subjects achieved weight loss by the time of their last visits. These two case studies, which differed in terms of sex, occupation, and dietary habits showed the importance of individualized nutrition intervention and forming an intimate relationship based on trust centered on prediabetic subjects. In conclusion, systematic collaboration within the clinical team is necessary, and social infrastructure should be prepared to fully realize the benefits of a systematic intervention program.

Characteristics of frequent emergency department users with type 2 diabetes mellitus in Korea.

AIMS/INTRODUCTION: Frequent emergency department (ED) visitors are medically vulnerable individuals. We identified the characteristics of "frequent ED users" among Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: We used the Health Insurance Review and Assessment Service National Patient Sample, which is a nationally representative sample. Patients (n = 109,412) with type 2 diabetes mellitus as a primary or secondary diagnosis at one of their visits were included. Individuals were classified into three groups according to the number of ED visits: frequent (≥4 visits), occasional (<4 visits) and non-users of the ED. The characteristics of the patients that distinguished frequent users from the other groups were investigated. RESULTS: Frequent ED users were mainly men (P < 0.001), with longer treatment duration (P < 0.001), more frequent comorbidities (cardiovascular and chronic kidney disease) and primary diagnosis made by surgery (P = 0.0028). They had higher mortality (P = 0.0085), longer hospitalization duration (P < 0.001), higher costs per visit (P < 0.001) and more often required medical protection (P < 0.001). These patients were treated more frequently with sulfonylurea, insulin, meglitinide and alpha-glucosidase inhibitors (P < 0.05). CONCLUSIONS: The present findings suggest that frequent users of the ED with type 2 diabetes mellitus have serious health conditions, a poor socioeconomic situation and tend to take some medicines (sulfonylurea, etc.), which often are associated with hypoglycemia. Attention should be given to therapy, and to patients with renal and cardiovascular diseases to decrease the dependency of these patients on the ED.

Long-term effects on glycaemic control and ß-cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial.

AIM: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of ß-cell function in people with type 2 diabetes mellitus (T2DM). METHODS: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive. RESULTS: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015). CONCLUSIONS: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in ß-cell function and glycaemic control over the long term, without serious adverse events.

Target achievement with maximal statin-based lipid-lowering therapy in Korean patients with familial hypercholesterolemia: A study supported by the Korean Society of Lipid and Atherosclerosis.

BACKGROUND: Data on treatment results of lipid-lowering therapy (LLT) in familial hypercholesterolemia (FH) are limited, particularly in Asian patients. HYPOTHESIS: We sought to evaluate the target achievement rate and associated variables in Korean patients with FH after maximal statin-based LLT. METHODS: We enrolled 146 patients with heterozygous FH, and 90 patients were finally analyzed. Patients were initially prescribed rosuvastatin 10 mg or atorvastatin 20 mg, and the regimen was adjusted to achieve the low-density lipoprotein cholesterol (LDL-C) target of 100 mg/dL. The primary evaluation point was the achievement rate of the LDL-C targets at 12 months: LDL-C < 100 mg/dL and ≥50% LDL-C reduction. The associations between clinical variables and target achievement were also analyzed. RESULTS: At 12 months, 58% of patients were receiving high-intensity regimens, whereas 46% were receiving combination therapy. The mean pre- and post-treatment LDL-C levels were 229 and 118 mg/dL, respectively. Twenty-eight percent of patients achieved LDL-C < 100 mg/dL, and 47% achieved ≥50% LDL-C reduction. Pretreatment LDL-C and high-intensity regimens indicated a negative tendency toward the attainment of LDL-C < 100 mg/dL. Conversely, pretreatment LDL-C and diabetes mellitus were positively associated with a higher rate of ≥50% LDL-C reduction. CONCLUSIONS: The target achievement of LDL-C < 100 mg/dL was low, and 50% LDL-C reduction was moderately achieved in Korean patients with FH receiving maximal statin-based LLT. Pretreatment LDL-C levels and diabetes mellitus were associated with target achievement. Our results provide rare and informative data on FH treatment in Asian patients.

Clinical characteristics and risk factors for retinal diabetic neurodegeneration in type 2 diabetes.

AIMS: To identify clinical characteristics and risk factors of retinal neurodegeneration represented by macular ganglion cell/inner plexiform layer (mGCIPL) thinning in patients with long-standing type 2 diabetes mellitus (T2DM). METHODS: Patients who had T2DM for >15 years were prospectively recruited from September 2014 to July 2015. Clinical data and samples were collected according to the Common Data Element and Standards of Procedure developed by the Korean Diabetes Association research council. Baseline characteristics included age, gender, family history, medical record of comorbidity, and microvascular complications. All patients underwent optical coherence tomography with automatic segmentation of the mGCIPL in six parafoveal regions. Multivariable regression analysis identified factors associated with mGCIPL thinning. RESULTS: Of 220 registered patients, 162 were included after ophthalmologic examination. The mean (SD) age was 65.0 (9.3) years, the mean duration of T2DM was 20.5 (4.0) years; mGCIPL thickness was 76.2 (8.5) µm. Hypertension, diabetic retinopathy, statin medication, estimated glomerular filtration rate, conduction velocity of the posterior tibial, peroneal, and sural nerves, and cardiac autonomic neuropathy (CAN) score were significantly correlated with mGCIPL thickness. Multivariate regression analysis showed that the CAN score (coefficient = -1.78, p = 0.001) and sural nerve velocity (coefficient = 0.458, p = 0.035) yielded a significant high regression correlation with mGCIPL thickness (overall R 2 = 0.46). CONCLUSIONS: This study demonstrated that various clinical features were associated with retinal neurodegeneration in T2DM. In particular, peripheral nerve conduction and autonomic nerve function were confirmed to be strong risk factors for mGCIPL thinning in patients with T2DM.

Effects of climatic variables on weight loss: a global analysis.

Several studies have analyzed the effects of weather on factors associated with weight loss. In this study, we directly analyzed the effect of weather on intentional weight loss using global-scale data provided by smartphone applications. Through Weather Underground API and the Noom Coach application, we extracted information on weather and body weight for each user located in each of several geographic areas on all login days. We identified meteorological information (pressure, precipitation, wind speed, dew point, and temperature) and self-monitored body weight data simultaneously. A linear mixed-effects model was performed analyzing 3274 subjects. Subjects in North America had higher initial BMIs than those of subjects in Eastern Asia. During the study period, most subjects who used the smartphone application experienced weight loss in a significant way (80.39%, p-value < 0.001). Subjects who infrequently recorded information about dinner had smaller variations than those of other subjects (ßfreq.users dinner*time = 0.007, p-value < 0.001). Colder temperature, lower dew point, and higher values for wind speed and precipitation were significantly associated with weight loss. In conclusion, we found a direct and independent impact of meteorological conditions on intentional weight loss efforts on a global scale (not only on a local level).