Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status. METHODS: Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors. RESULTS: Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19-1.58) for all-cause mortality and 1.63 (95% CI, 1.29-2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03-1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08-2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively. CONCLUSIONS: The findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR's fluctuations over time should be further focused.

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes.

BACKGROUND: Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes. METHODS: This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39-1.30 mIU/L; medium-normal, 1.30-2.09 mIU/L; high-normal, 2.09-4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality. RESULTS: During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07-1.61) and CVD (1.52; 1.08-2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12-1.73) and CVD (1.69; 1.17-2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants. CONCLUSION: Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.

Capecitabine-induced severe diabetes and hypokalemia: a case report.

BACKGROUND: Capecitabine is widely used in chemotherapy for breast, colorectal, and gastric cancers. The frequent adverse reactions of capecitabine mainly include gastrointestinal side effects, anemia, and cardiovascular toxicity. Here, we report a rare case of severe hyperglycemia and hypokalemia during long-term treatment with capecitabine. CASE PRESENTATION: A 48-year-old Chinese female was hospitalized with the complaint of breathlessness and weakness after activity, for 1 month. Her past history is significant for a diagnosis of right-sided breast cancer 7 years ago. She underwent right mastectomy, following which capecitabine was started 1.5 years prior to the current admission as part of her primary treatment at the discovery of systemic osseous metastasis. Her fasting plasma glucose and hemoglobin A1c levels were quite normal 7 months ago but increased to 15.3 mmol/L and 11.2%, respectively, at the present admission. Her serum potassium level was as low as 2.5 mmol/L. Plasma autoantibodies related to islets and insulin were all negative. Capecitabine was discontinued, and an insulin pump and potassium supplement were given after admission. Her blood sugar and potassium levels returned to their normal ranges soon. Self-injection of insulin was withdrawn completely at 2 months after discharge, and no oral hypoglycemic agents were added. Her plasma glucose and electrolyte levels were at normal levels at her 1-year follow-up. CONCLUSION: Glucose intolerance and hypokalemia may be rare but serious adverse effects during long-term chemotherapy with capecitabine.

AGEs-induced MMP-9 activation mediated by Notch1 signaling is involved in impaired wound healing in diabetic rats.

AIMS: To elucidate the relationship between advanced glycation end products (AGEs), Notch1 signaling, nuclear factor-kappa B (NF-κB), and matrix metalloproteinase-9 (MMP-9) in diabetic wound healing in vitro and in vivo. METHODS: We incubated primary keratinocytes with AGEs alone or AGEs along with γ-secretase inhibitor DAPT, and established diabetic rat wound model by intraperitoneal streptozotocin treatment. The Notch1 signaling components and MMP-9 expression were detected by qPCR, western blotting and gelatin zymography. RESULTS: The exposure of primary keratinocytes to AGEs led to a significant increase in Notch intracellular domain (NICD), Delta-like 4 (Dll4), and Hes1; however, Notch1 expression was inhibited by the RAGE siRNA. Furthermore, MMP-9 activation was up-regulated, secondary to AGEs treatment. In contrast, increased MMP-9 expression by AGEs-stimulation was eliminated after treatment with DAPT. NF-κB activation participated in the Notch1-modulated MMP-9 expression. Notably, in the diabetic animal model, inhibition of the Notch signaling pathway with DAPT attenuated NICD and MMP-9 overexpression, improved collagen accumulation, and ultimately accelerated diabetic wound healing. CONCLUSIONS: These findings identified that activation of the Notch1/NF-κB/MMP-9 pathway, in part, mediates the repressive effects of AGEs on diabetic wound healing and that targeting this pathway may be a potential strategy to improve impaired diabetic wound healing.

A Chinese Family with Familial Dysalbuminemic Hyperthyroxinemia (FDH) due to R242H Mutation on Human Albumin Gene: Reevaluating the Role of FDH in Patients with Asymptomatic Hyperthyroxinemia.

OBJECTIVE: Familial dysalbuminemic hyperthyroxinemia (FDH) has now become an established cause for spurious asymptomatic hyperthyroxinemia. Several different codon mutations on albumin gene had been identified. We here provided an established but rarely reported heterozygous mutation based on gene sequencing results from a Chinese family. METHODS: The proband is a 14-year-old girl with light goiter and asymptomatic clinical presentations, whose thyroid function test by a one-step immunoassay showed increased free thyroxine (FT4) and free triiodothyronine (FT3) but nonsuppressed thyrotropin (TSH). All thyroid auto-antibodies were in the normal range. Blood samples were collected from her and most of her immediate family members for target gene sequencing and verification. RESULTS: Hyperthyroxinemia was also confirmed in the proband's mother and one of her uncles and his son. In the proband and these three pedigrees, the high-throughput gene screening sequencing and the following Sanger sequencing disclosed a heterozygous mutation in the albumin gene, which located in its exon 7 (c.725G > A), and correspondingly leads to an arginine replacement with a histidine (R242H) in its protein. This is an established mutation named as R218H if present without signal peptide sequence. CONCLUSIONS: For patients with asymptomatic hyperthyroxinemia, FDH should be clinically excluded before embarking on further investigations for other specific causes.

[Composition analysis of volatile oil of Asarum heterotropoides var. mandshuricum extracted by three different methods].

OBJECTIVE: To study the differences of the constituents of the volatile oil from Asarum heterotropoides var. mandshuricum with three different extracted methods. METHODS: Volatile oil from Asarum heterotropoides var. mandshuricum was extracted by steam distillation, supercritical carbon dioxide extraction and supercritical carbon dioxide extraction followed by concentration under pressure to remove volatile components, respectivily. GC-MS was utilized to analyze the components of volatile oil. RESULTS: The volatile oil from Asarum heterotropoides var. mandshuricum extracted by steam distillation and supercritical carbon dioxide extraction method contained 36 ingredients, 16 of which were the same, but different in amount. 11 kinds of non-volatile components of the volatile oil from Asarum heterotropoides var. mandshuricum were identified as the main components with supercrtical carbon dioxide extraction followed by concentration under reduced pressure, which were mainly fats and oils. CONCLUSION: The common components and their relative contents of the volatile oil from Asarum heterotropoides var. mandshuricum are obtained and compared with different extraction methods. It's the first time to extract the volatile components in the volatile oil from Asarum heterotropoides var. mandshuricum by supercritical carbon dioxide extraction, which provides the basis for Chinese herbal medicinal ingredients and quality control of the Asarum to some extent.