Clinical significance of skin autofluorescence for diabetic macroangiopathy and comparison with conventional markers of atherosclerosis: a cross-sectional and prospective study.

Background: Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear. Methods: We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9. Results: SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke. Conclusion: Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00608-8.

Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

AIMS: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. METHODS: Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. RESULTS: In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. CONCLUSIONS: LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Dyslipidemia in diabetic kidney disease classified by proteinuria and renal dysfunction: A cross-sectional study from a regional diabetes cohort.

AIMS/INTRODUCTION: Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied. MATERIALS AND METHODS: Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 in the absence or presence of urinary albumin-to-creatinine ratio >300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay. RESULTS: The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria. CONCLUSIONS: Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Myxedema Coma Following the Administration of Gonadotropin-releasing Hormone Agonist Complicated by Acute Pancreatitis.

Gonadotropin-releasing hormone (GnRH) agonists have been used for the treatment of various diseases. Although autoimmune thyroid disease has been reported as a rare complication of these agents, the symptoms are almost always transient and non-life-threatening. We herein report a rare case of an 83-year-old man receiving GnRH agonist treatment for prostate cancer who developed myxedema coma complicated by acute pancreatitis. This is the first report of myxedema coma potentially associated with a GnRH agonist. The follow-up of the thyroid function is necessary for patients undergoing treatment with GnRH agonists, especially those known to have or to be susceptible to autoimmune thyroid disease.

Non-occlusive Mesenteric Ischemia with Diabetic Ketoacidosis and Lactic Acidosis Following the Administration of a Sodium Glucose Co-transporter 2 Inhibitor.

We herein describe a patient with non-occlusive mesenteric ischemia (NOMI) potentially associated with the administration of a sodium glucose co-transporter 2 (SGLT2) inhibitor. A 60-year-old man with type 1 diabetes was transferred to our hospital due to vomiting and respiratory distress. He was treated with insulin, metformin and a SGLT2 inhibitor, which had recently been added. He was diagnosed with intestinal ischemia complicated by diabetic ketoacidosis and lactic acidosis. Urgent exploratory surgery was performed, and the gangrenous bowel was resected. Histological findings confirmed the diagnosis of NOMI. The administration of SGLT2 inhibitors therefore requires certain exceptions for type 1 diabetes and cautious monitoring for the occurrence of these possible adverse effects.