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 Outcomes of COVID-19 Patients with Type 2 Diabetes: A Population-Based Study in Korea.

BACKGROUND: The aim of this study was to evaluate clinical outcomes in coronavirus disease 2019 (COVID-19) positive patients with type 2 diabetes compared to those without diabetes in Korea. METHODS: We extracted claims data for patients diagnosed with COVID-19 from the National Health Insurance Service database in Korea from January 20, 2020 to March 31, 2020. We followed up this cohort until death from COVID-19 or discharge from hospital. RESULTS: A total of 5,473 patients diagnosed with COVID-19 were analyzed, including 495 with type 2 diabetes and 4,978 without diabetes. Patients with type 2 diabetes were more likely to be treated in the intensive care unit (ICU) (P<0.0001). The incidence of inhospital mortality was higher in patients with type 2 diabetes (P<0.0001). After adjustment for age, sex, insurance status, and comorbidities, odds of ICU admission (adjusted odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.49; P=0.0416) and in-hospital mortality (adjusted OR, 1.90; 95% CI, 1.13 to 3.21; P=0.0161) among patients with COVID-19 infection were significantly higher in those with type 2 diabetes. However, there was no significant difference between patients with and without type 2 diabetes in ventilator, oxygen therapy, antibiotics, antiviral drugs, antipyretics, and the incidence of pneumonia after adjustment. CONCLUSION: COVID-19 positive patients with type 2 diabetes had poorer clinical outcomes with higher risk of ICU admission and in-hospital mortality than those without diabetes. Therefore, medical providers need to consider this more serious clinical course when planning and delivering care to type 2 diabetes patients with COVID-19 infection.

Metformin and Gastrointestinal Cancer Development in Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea.

INTRODUCTION: Clinical studies have produced conflicting results on the effects of metformin on gastrointestinal cancer development. We aimed to investigate the association between metformin use and stomach, colon, liver, and pancreatic cancer development among patients with newly diagnosed, drug-naïve type 2 diabetes. METHODS: This retrospective study evaluated propensity score-matched patients with newly diagnosed type 2 diabetes from the Korean National Health Insurance Service database. Metformin users were categorized into tertiles according to the cumulative dose or duration of metformin treatment, and the risks of gastrointestinal cancers were compared. RESULTS: Metformin users had reduced risks of developing stomach cancer (hazard ratio [HR]: 0.841, 95% confidence interval [CI]: 0.797-0.887), colon cancer (HR: 0.865, 95% CI: 0.822-0.91), and liver cancer (HR: 0.709, 95% CI: 0.675-0.746; P < 0.001). However, metformin users did not have a reduced overall risk of pancreatic cancer (HR: 1.335, 95% CI: 1.209-1.475; P < 0.001). The risks tended to decrease at higher cumulative doses and durations of metformin use, with significantly reduced risks of all 4 cancers at the highest cumulative dose (≥1,200,000 mg) and the longest duration (≥2,000 days) of metformin use. DISCUSSION: This population-based data suggest that metformin could be associated with reductions in the risks of stomach, colon, and liver cancers, as well a reduced risk of pancreatic cancer in some subgroups. Metformin has benefit as a first-line treatment for type 2 diabetes mellitus. A further role in cancer risk reduction could be studied in controlled trials.

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.

Trends in Hyperglycemic Crisis Hospitalizations and in- and out-of-Hospital Mortality in the Last Decade Based on Korean National Health Insurance Claims Data.

BACKGROUND: Hyperglycemic crisis is a metabolic emergency associated with diabetes mellitus. However, accurate epidemiologic information on cases of hyperglycemic crisis in Korea remains scarce. We evaluated trends in hyperglycemic crisis hospitalizations and in- and out-of-hospital mortality in Korea. We also predicted future trends. METHODS: We extracted claims data with hyperglycemic crisis as the principal diagnosis from the National Health Insurance Service database in Korea from January 2004 to December 2013. We investigated the numbers of claims with hyperglycemic crisis and identified trends in hyperglycemic crisis based on those claims data. We predicted future trends by statistical estimation. RESULTS: The total annual number of claims of hyperglycemic crisis increased from 2,674 in 2004 to 5,540 in 2013. Statistical analysis revealed an increasing trend in hyperglycemic crisis hospitalizations (P for trend <0.01). In contrast, the hospitalization rate per 1,000 diabetes cases showed a decreasing trend (P for trend <0.01) during this period. The mortality rate per 1,000 diabetes cases also showed a decreasing trend (P for trend <0.0001). However, no distinct linear trend in the case-related fatality rate at <60 days over the last decade was observed. The predicted number of annual claims of hyperglycemic crisis will increase by 2030. CONCLUSION: The number of hyperglycemic crisis hospitalizations in Korea increased in the last decade, although the hospitalization rate per 1,000 diabetes cases and mortality rate decreased. Also, the predicted number of annual claims will increase in the future. Thus, it is necessary to establish long-term healthcare policies to prevent hyperglycemic crisis.

Calpain-10 and Adiponectin Gene Polymorphisms in Korean Type 2 Diabetes Patients.

BACKGROUND: Genetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients. METHODS: Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes. RESULTS: Among calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion. CONCLUSION: Variations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.

Association between triglyceride glucose index and arterial stiffness in Korean adults.

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. METHODS: A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. RESULTS: The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. CONCLUSION: The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

[A Case of Rectal Syphilis Incidentally Found at Regular Medical Check-up].

Syphilis is a rare disease in the rectum. It is difficult to diagnose because the characteristics of the rectal syphilis rectal lesion are highly varied. The endoscopic findings of rectal syphilis are proctitis, ulcers, and masses. If rectal syphilis is suspected to be the cause for rectal lesions, it is important for physicians to consider the sexual history and sexual orientation of the patient. We report a case of incidental rectal syphilis in a 41-year-old man diagnosed during a regular medical check-up.