Association of Protein Z with Prediabetes and Type 2 Diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease. Early detection of prediabetes is important to reduce the risk of T2DM. Some cytokines are known to be associated with T2DM. Therefore, we aimed to identify cytokines as novel biomarkers of glucose dysmetabolism. METHODS: The first stage of the study included 43 subjects (13 subjects with newly diagnosed T2DM, 13 with prediabetes, and 16 with normoglycemia) for cytokine microarray analysis. Blood samples of the subjects were assessed for 310 cytokines to identify potential indicators of prediabetes. The second stage included 142 subjects (36 subjects with T2DM, 35 with prediabetes, and 71 with normoglycemia) to validate the potential cytokines associated with prediabetes. RESULTS: We identified 41 cytokines that differed by 1.5-fold or more in at least one out of the three comparisons (normoglycemia vs. prediabetes, normoglycemia vs. T2DM, and prediabetes vs. T2DM) among 310 cytokines. Finally, we selected protein Z (PROZ) and validated this finding to determine its association with prediabetes. Plasma PROZ levels were found to be decreased in patients with prediabetes (1,490.32±367.19 pg/mL) and T2DM (1,583.34±465.43 pg/mL) compared to those in subjects with normoglycemia (1,864.07±450.83 pg/mL) (P<0.001). There were significantly negative correlations between PROZ and fasting plasma glucose (P=0.001) and hemoglobin A1c (P=0.010). CONCLUSION: PROZ levels were associated with prediabetes and T2DM. We suggest that PROZ may be a promising biomarker for the early detection of prediabetes. Further large-scale studies are needed to evaluate the relationship and mechanism between PROZ and prediabetes and T2DM.

Clinical Correlates of Frontal Intermittent Rhythmic Delta Activity Without Structural Brain Lesion.

Frontal intermittent rhythmic delta activity (FIRDA), rhythmic slow wave pattern lasting several seconds over the anterior leads of electroencephalography (EEG), has been reported in a wide variety of clinical conditions. We investigated the clinical significance of FIRDA without structural brain lesions. We reviewed 7689 EEGs between October 2017 and September 2019 at a university hospital. Patients (age >18 years) who were confirmed to have "nonsignificant neuroimaging" were examined. Clinical data were retrospectively collected, and the estimated cause was carefully decided. We found 83 FIRDA among 7689 EEGs (1.08%). After patients with any structural lesion identified on neuroimaging were excluded, 37 FIRDAs were reviewed. There were 20 (51.35%) patients of metabolic encephalopathy. Six patients showed FIRDA due to neurodegenerative disease (16.21%). In addition, we found 6 (16.21%) of neurodegenerative disease and 5 (13.51%) of hypoxic encephalopathy (cardiac arrest). Four (16.21%) patients were related to systemic infection (10.81%), whereas 2 were related to encephalitis (5.40%). We demonstrated several potential etiologies, including metabolic encephalopathy, neurodegenerative disease, hypoxic encephalopathy, and infections, which should be considered in the case of FIRDA without structural brain lesions.

Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus.

This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.

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.

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Comparison of Serum PCSK9 Levels in Subjects with Normoglycemia, Impaired Fasting Glucose, and Impaired Glucose Tolerance.

We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations in individuals with normoglycemia, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). This was a pilot, cross-sectional study including 92 individuals who had not been diagnosed with or treated for diabetes. We measured PCSK9 levels in three groups of subjects; namely, normoglycemia (n=57), IFG (n=21), and IGT (n=14). Individuals with IFG and IGT showed higher PCSK9 concentrations than those in the normoglycemic group, with the highest serum PCSK9 concentrations found in individuals with IGT (55.25±15.29 ng/mL for normoglycemia, 63.47±17.78 ng/mL for IFG, 72.22±15.46 ng/mL for IGT, analysis of variance P=0.001). There were no significant differences in high- or low-density lipoprotein cholesterol among groups. Serum PCSK9 levels are increased in patients with prediabetes compared to subjects with normoglycemia.

Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011).

BACKGROUND: Although the involvement of obesity in metabolic disorders is well known, leg fat depot influences on albuminuria have not been determined. METHODS: This population-based, cross-sectional study used a nationally representative sample of 2,076 subjects aged ≥20 years from the Korea National Health and Nutrition Examination Surveys of 2008 to 2011. The ratio of leg fat to total fat (LF/TF ratio) was assessed by dual X-ray absorptiometry, and albuminuria was defined as more than one positive dipstick test or an albumin-to-creatinine ratio of ≥30 mg/g. RESULTS: Individuals whose LF/TF ratio was in the lowest tertile showed a higher proportion of albuminuria than those in the highest tertile (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.01 to 3.96; P<0.001). This association was observed in both sexes, all age groups, and all subgroups stratified by body mass index, waist circumference, homeostasis model assessments of insulin resistance, and the presence of metabolic syndrome (all, P<0.05). Multiple logistic regression analyses also demonstrated that the lowest LF/TF ratio was independently associated with albuminuria risk (OR, 1.55 to 2.16; all, P<0.05). In addition, the risk of albuminuria was higher in sarcopenic individuals with lower LF/TF ratios than in the highest LF/TF ratio subjects without sarcopenia (OR, 3.73; 95% CI, 2.26 to 6.13). CONCLUSION: A lower LF/TF ratio was associated with an increased risk of albuminuria independent of obesity, insulin resistance, and metabolic syndrome, and when combined with sarcopenia, the albuminuria risk synergistically increased. Hence, our findings may have implications to improve risk stratification and recommendations on body fat distribution in the general population.

Patient Understanding of Hypoglycemia in Tertiary Referral Centers.

BACKGROUND: Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia. METHODS: A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia. RESULTS: Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits. CONCLUSION: Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Clinical Characteristics of Patients with Adrenal Insufficiency in a General Hospital.

BACKGROUND: Adrenal insufficiency (AI) is a life-threatening disorder caused by the deficiency of adrenal steroid hormones. This retrospective cross-sectional study investigated the characteristics of patients with AI in Korea. METHODS: All consecutive patients with suspected AI who received care at a tertiary referral center in Korea in 2014 and underwent adrenocorticotropic hormone stimulation or insulin-tolerance testing were identified through a review of medical charts. Patients diagnosed with AI were enrolled. Their demographic, clinical, and treatment details were extracted. RESULTS: Of 771 patients with suspected AI, 183 (23.7%) received a definitive diagnosis. The most common reason for testing was the presence of suspicious AI-related symptoms (30.0%), followed by a history of steroid medications (23.5%). Their mean age was 66.7 years, and females predominated (67.8%). The most common symptoms were general weakness, anorexia, arthralgia, and fever. Approximately half (53.6%) had a history of steroid use. Hydrocortisone was the most common treatment (71.6%), with most patients taking a 30 mg dose (44.2%). The most common dose frequency was twice a day (78.6%). Fourteen patients were treated for adrenal crisis (n=10, 5.5%) or an intercurrent illness (n=4, 2.2%). CONCLUSION: AI may have been caused by steroid medication use in many of the patients included in this study. The detection of AI can be improved by careful history-taking and being alert to the possibility that a patient has used steroids.