Hyperglycemia Increases Muscle Blood Flow and Alters Endothelial Function in Adolescents with Type 1 Diabetes

Department of Pediatrics, West Virginia University, Charleston, WV 25302, USA.
Experimental Diabetes Research (Impact Factor: 4.33). 06/2012; 2012(5):170380. DOI: 10.1155/2012/170380
Source: PubMed


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.

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Available from: Robert Hoffman, Aug 20, 2015
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    • "Eleven patients then participated in an insulin clamp study to assess the effects of glucose normalization and hyperglycemia. Results on this study have been previously reported [16]. Subjects were then placed on a continuous 24- hour glucose monitor (Medtronic Guardian, Fridley MN) for 3 days after which the monitor was returned and the data was downloaded using the Medtronic Carelink website to determine the mean glucose level and standard deviation. "
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    ABSTRACT: 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.
    12/2013; 2013(6):876547. DOI:10.1155/2013/876547
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    • "There is a compelling evidence that hypertension could significantly increase the risk of cardiovascular diseases in diabetic patients [24], indicating an urgent need for identifying hypertension susceptible genes in this subset of individuals [25]. Moreover, dysfunctional endothelium-dependent vasodilation and impaired nitric oxide bioavailability have been reported in diabetes [26–28], raising the possibility that apelin may interact with diabetes in the regulation of blood pressure. In this context, another aim of the current study was to examine the effect of APLN genetic variants on hypertension in patients with diabetes. "
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    ABSTRACT: Background: Apelin, the endogenous ligand for the APJ receptor, has a potent hypotensive effect via a nitric oxide-dependent mechanism in vivo. The aim of the study was to investigate the association between the common variants of apelin gene (APLN) and hypertension, which was reported recently in a Chinese Han population with and without diabetes. Methods: Three single nucleotide polymorphisms (SNPs) on APLN were genotyped in 3156 diabetic patients and 3736 nondiabetic individuals. For non-diabetic subjects, 1779 were enrolled in stage 1 and 1757 were recruited for validation. A meta-analysis combining the two stages was carried out to obtain the overall effect. Results: In diabetic patients, no significant associations of the three SNPs with hypertension were observed. In contrast, we found that rs2235306 was associated with hypertension in non-diabetic males after adjusting for covariates (OR = 1.19, P = 0.039) while rs2235307 and rs3115759 displayed no evidence of association in both genders. One haplotype, C-C-A, also showed an association with hypertension (OR = 1.47, P = 0.032) only in men. However, analysis in stage 2 and meta-analysis did not support these findings. Conclusions: We conclude that common variants on APLN are not associated with the prevalence of hypertension in the Chinese.
    Experimental Diabetes Research 12/2012; 2012:917496. DOI:10.1155/2012/917496 · 4.33 Impact Factor
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    ABSTRACT: Studies on the alterations of liver and kidney function parameters in patients with diabetic ketoacidosis (DKA) and diabetic ketosis (DK) were limited. Participants with DKA, DK, non-DK, and healthy controls were enrolled in the current study. Parameters of liver and kidney function were measured and evaluated. The patients with DKA had higher levels of plasma glucose, hemoglobin A1c (HbA1c), uric acid, and creatinine but lower levels of transferases and protein compared with the other three groups (P < 0.05 for all). The patients with DK had higher levels of plasma glucose and HbA1c but lower levels of glutamyl transpeptidase and protein compared with the non-DK and control groups (P < 0.05). Prealbumin levels were significantly reduced in the severe DKA patients compared with the mild/moderate DKA patients. Serum prealbumin levels were correlated with albumin levels (r = 0.401, P = 0.010), HCO3 (r = 0.350, P = 0.027), and arterial pH (r = 0.597, P < 0.001) in the DKA patients. A diagnostic analysis showed that lower prealbumin levels significantly reflected the presence of hyperglycemic emergencies (P < 0.001). Liver and kidney function parameters deteriorated, especially in DKA. Prealbumin levels can be of value in detecting the presence of hyperglycemic crisis. This clinical trial is registered with ChiCTR-OCH-12003077.
    Journal of Diabetes Research 10/2013; 2013:967097. DOI:10.1155/2013/967097 · 2.16 Impact Factor
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