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Abstract-Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1Ϯ12.

Aims/hypothesis. Maternal fuel metabolism is known to exert long range effects on the later development of children of diabetic mothers. Recently cardiovascular disease in adult life has been linked retrospectively with foetal malnutrition. The aim of this study was to identify whether markers for fuel-related cardiovascular programming exist for the offspring of diabetic pregnancy. Methods. Sixty-one children aged 5 to 11 years, of mothers with Type I (insulin-dependent) diabetes mellitus were compared with 57 randomly selected control children of non-diabetic mothers similar in age, sex and social class. Fasting blood was taken for plasma glucose, insulin, lipids, IGF-1, plasminogen activating inhibitor 1 (PAI-1) and the adhesion molecules ICAM-1, VCAM-1 and E-Selectin. Results. Fasting glucose and insulin were similar in the two groups. Differences existed between the offspring of diabetic and non-diabetic pregnancies (mean ± SD) for total cholesterol (4. with diabetic pregnancy is the consequence of foetal hyperinsulinism secondary to excess maternal glucose and other fuels. While subsequent data would generally support this concept, the relatively few studies which have examined the question are poorly comparable and focus almost exclusively on growth and glucose regulation [3,4]. Confounding factors include variation in the number of subjects, year of birth, age at follow up, type of diabetes (pregestational, gestational), adequate control subjects and assessment of morbidities. During the intervening four decades, the management of pregnant women and their newborns has improved markedly.Recently others have shown provocative epidemiological evidence that coronary heart disease, and several other chronic adult diseases have their originsThe proposal that maternal fuel metabolism might exert long range effects on human development was first suggested more than 40 years ago [1]. The hypothesis, with minor modification [2], is now widely accepted and envisages that excess foetal growth associated

NCT01463579. (results), https://clinicaltrials.gov/.

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection ( Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

In vivo bedside assessment of endothelium-dependent vasodilatation is an independent predictor of mortality in the critically ill. We have shown it to be superior to other validated severity of illness scores with high sensitivity and specificity.

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1. Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA), administered intra-arterially, has been reported to improve endothelium-dependent vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double-blind, placebo-controlled, cross-over study, we investigated the potential for intravenous ascorbic acid to modify the endothelial response to acute systemic hyperglycaemia in humans. 2. Nine healthy male volunteers were recruited from the hospital staff. Endothelial function was determined by measuring the forearm blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and endothelium-independent (EID) vasodilators. The endothelial function index (EFI) was derived from the ratio of ED and EID vasodilatation. Haemodynamic and endothelial function measurements were performed at baseline and then repeated 2 h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid prior to the initiation of hyperglycaemia. 3. After systemic hyperglycaemia with placebo pretreatment, the EFI fell from 1.08 +/- 0.21 to 0.74 +/- 0.13 (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When subjects were pretreated with ascorbic acid, the EFI was not affected by hyperglycaemia (1.11 +/- 0.21 to 1.12 +/- 0.17; P = 0.938). This difference between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate concentrations decreased during hyperglycaemia and correlated directly with the reduction in the EFI (r = 0.798; P < 0.001). 4. Pretreatment with an intravenous bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in clinical situations where acute hyperglycaemia may be a complication.