Ascorbic acid blocks hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes.

OBJECTIVE: To determine whether acute ascorbic acid infusions alter the effect of hyperglycemia on endothelial function in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: The forearm blood flow (FBF) reactive hyperemic response to 5 min of upper arm occlusion was studied in eight adolescents with type 1 diabetes during euglycemic and hyperglycemic insulin clamp (40 mU/m2/min) with and without ascorbic acid infusion (3 mg/min). RESULTS: The ratio of post- to preocclusion FBF decreased during hyperglycemia without ascorbic acid (p = 0.013), but did not change during hyperglycemia with ascorbic acid. The changes during hyperglycemia were different between the two studies (p = 0.038). Similar results were found when the percent change in forearm vascular resistance following occlusion was assessed. CONCLUSIONS: These results indicate that antioxidant treatment with ascorbic acid blocks acute hyperglycemic impairment of endothelial function in adolescents with type 1 diabetes.

Epidemiology and autopsy findings of 500 drowning deaths.

INTRODUCTION: Drowning is a significant public health problem worldwide and the WHO reported that drowning is the world's third leading unintentional injury death. Nevertheless, there is still uncertainty regarding the estimate of local and global drowning deaths. In addition, the postmortem diagnosis of drowning is challenging and the physiological mechanisms of death by drowning are complex and not very well understood. PURPOSE: To analyze a large series of bodies retrieved from the water in Connecticut (U.S.) in order to compare epidemiologic and toxicological data with those of the literature, as well as to examine the weights of the lungs and brains in drowning deaths. MATERIAL AND METHOD: We conducted a descriptive, retrospective, population-based analysis of all bodies retrieved from the water and subjected to a forensic autopsy at the Office of the Chief Medical Examiner in Connecticut (2008-2020, n = 500). Variables collected were sex, age, date of death, location of drowning, season, type of water, cause of death, manner of death, circumstances of death, signs of decomposition, BMI, brain weight, lung weight, presence of pulmonary edema, stomach contents, and toxicological analysis. RESULTS: The death rates of drownings in Connecticut ranges from 0.75 to 1.28/100,000/year. They occurred predominantly in males (73.4%) and most were accidents (75.6%), though this gender difference diminishes in suicides (55.4% of males). Sex distribution is also different in bathtub drownings, where women drown more frequently (67.3%). Weights of the brains (p = 0.013) and lungs (p < 0.001) were higher in saltwater drownings. CONCLUSIONS: Drowning is more frequently an accident involving men, except for suicides where there is only a slight difference among sex. Heavy lungs and cerebral edema continue to be identified in numerous drowning deaths. These anatomic findings, however, must still be interpreted in the context of the entire case investigation. Weights of the brains and lungs are higher in salt water, although these organs' weights are mostly dependent on other variables such as BMI and decomposition.

Glycemic variability predicts inflammation in adolescents with type 1 diabetes.

BACKGROUND: Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. METHODS: This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c×duration area under the curve (A1cDur). RESULTS: Seventeen adolescents (8 F/9M; age, 13.1±1.6 years (mean±SD); duration, 4.8±3.8 years, BMI, 20.3±3.1 kg/m2; A1c, 8.3±1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n=13, r=0.61, p=0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r=0.66, p=0.006). TAOC increased as glucose standard deviation increased (r=0.63, p=0.028). CONCLUSIONS: Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress.

Effects of glucose control and variability on endothelial function and repair in adolescents with type 1 diabetes.

Background. Endothelial dysfunction and increased inflammation are precursors of cardiovascular disease in type 1 diabetes (T1D) and occur even in adolescents with T1D. The goal of this study was to determine the relationship of endothelial dysfunction to various measures of glycemia. Research Design and Methods. Forearm blood flow (FBF, venous occlusion plethysmography) was measured before and after 5 min of upper arm vascular occlusion in 17 adolescents with uncomplicated type 1 diabetes. Endothelial function was assessed as postocclusion FBF and forearm vascular resistance (FVR, mean arterial pressure/FBF). Fasting glucose, 72 hour mean glucose and standard deviation from continuous glucose monitoring, hemoglobin A1c, and hemoglobin A1c by duration area under the curve were used to assess immediate, short-term, and intermediate- and long-term glycemia. Results. Postocclusion FBF (r = -0.53, P = 0.030) negatively correlated and postocclusion FVR positively correlated (r = 0.52, P = 0.031) with hemoglobin A1c levels. FVR was positively associated with log 3 day mean glucose (r = 0.55, P = 0.027). Postocclusion FBF (2.8 ± 1.1 versus 3.4 ± 0.5 mL/dL/min, mean ± SE, P = 0.084) tended to be lower and FVR (31.4 ± 10.4 versus 23.9 ± 4.4 mmHg dL min/mL, P = 0.015) was significantly higher in subjects with hemoglobin A1c above the median (8.3%) compared to those with lower hemoglobin A1c levels. Conclusions. These results demonstrate that poor intermediate-term glycemic control is associated with impaired endothelial function.

Hyperglycemia increases muscle blood flow and alters endothelial function in adolescents with type 1 diabetes.

Alterations of blood flow and endothelial function precede development of complications in type 1 diabetes. The effects of hyperglycemia on vascular function in early type 1 diabetes are poorly understood. To investigate the effect of hyperglycemia on forearm vascular resistance (FVR) and endothelial function in adolescents with type 1 diabetes, FVR was measured before and after 5 minutes of upper arm arterial occlusion using venous occlusion plethysmography in (1) fasted state, (2) euglycemic state (~90 mg/dL; using 40 mU/m(2)/min insulin infusion), and (3) hyperglycemic state (~200 mg/dL) in 11 adolescents with type 1 diabetes. Endothelial function was assessed by the change in FVR following occlusion. Seven subjects returned for a repeat study with hyperglycemia replaced by euglycemia. Preocclusion FVR decreased from euglycemia to hyperglycemia (P = 0.003). Postocclusion fall in FVR during hyperglycemia was less than during euglycemia (P = 0.002). These findings were not reproduced when hyperglycemia was replaced with a second euglycemia. These results demonstrate that acute hyperglycemia causes vasodilation and alters endothelial function in adolescents with type 1 diabetes. In addition they have implications for future studies of endothelial function in type 1 diabetes and provide insight into the etiology of macrovascular and microvascular complications of type 1 diabetes.