Vasodilation and increased blood flow are characteristic early vascular responses to acute hyperglycemia and tissue hypoxia. In hypoxic tissues these vascular changes are linked to metabolic imbalances associated with impaired oxidation of NADH to NAD+ and the resulting increased ratio of NADH/NAD+. In hyperglycemic tissues these vascular changes also are linked to an increased ratio of NADH/NAD+, in this case because of an increased rate of reduction of NAD+ to NADH. Several lines of evidence support the likelihood that the increased cytosolic ratio of free NADH/NAD+ caused by hyperglycemia, referred to as pseudohypoxia because tissue partial pressure oxygen is normal, is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural function and plays an important role in the pathogenesis of diabetic complications. These effects of hypoxia and hyperglycemia-induced pseudohypoxia on vascular and neural function are mediated by a branching cascade of imbalances in lipid metabolism, increased production of superoxide anion, and possibly increased nitric oxide formation.
Abdominal liposuction does not significantly improve obesity-associated metabolic abnormalities. Decreasing adipose tissue mass alone will not achieve the metabolic benefits of weight loss.
Objective. To assess the antihypertensive efficacy and safety of the combination of the direct renin inhibitor aliskiren and ramipril in patients with diabetes and hypertension. Methods. In this double-blind, multicentre trial, 837 patients with diabetes mellitus and hypertension (mean sitting diastolic blood pressure [BP] > 95 and < 110 mmHg) were randomised to once-daily aliskiren (150 mg titrated to 300 mg after four weeks; n=282), ramipril (5 mg titrated to 10 mg; n=278) or the combination (n=277) for eight weeks. Efficacy variables were cuff mean sitting diastolic BP (msDBP) and mean sitting systolic BP (msSBP); 24-hour ambulatory BP, plasma renin activity (PRA) and plasma renin concentration (PRC) were also assessed.
The current study examined the role of health beliefs in diabetic regimen adherence and metabolic control. The subjects were 143 insulin-dependent diabetic outpatients, including 54 from a university juvenile diabetes care clinic with a mean age of 18 and 89 from a private practice clinic with a mean age of 37. Subject age and knowledge about diabetes were statistically controlled for in the multiple regression equations used to analyze the data. Overall, health beliefs accounted for a statistically significant portion of the variance in both self-reported adherence and metabolic control, as measured by level of glycosylated hemoglobin. For older patients from the private practice clinic, the most important aspects of health beliefs related to both reported adherence and metabolic control were those associated with the perceived benefits of adhering to the diabetic regimen. For younger patients from the university clinic, although perceived costs figured most prominently in their reports of adherence, perceived severity and susceptibility were the most important health beliefs associated with their actual levels of metabolic control. These findings suggest that health beliefs may play an important role in diabetic regimen adherence and metabolic control.Diabetes mellitus affects over 5 million Americans (Karam, 1981). Treatment of this chronic condition requires careful regulation of diet, exercise, and (often) drug or insulin dosage, along with frequent monitoring of blood or urine sugar levels to maintain blood glucose levels within as near normal a range as possible. Most diabetics manage their disease well enough to avoid serious effects from acute complications. However, there are a number of long-term complications associated with chronically elevated blood glucose levels (Brownlee & Cerami, 1981;Pirart, 1978) that make diabetes the leading cause of blindness in the United States and contribute to a markedly shortened life span among diabetics (Lipsett, 1980; U.S. Department of Health, Education, and Welfare, 1979). Although diabetic blood glucose levels are influenced by physiological factors, behavioral adherence to the complicated diabetes care regimen is a major determinant of blood sugar control. 1 As with other medical regimens, adherence to the diabetic regimen is often inadequate (Cerkoney& Hart, 1980;Ruff, 1983;Wiholm, This article is based on a master's thesis by the first author conducted under the supervision of the second author. Thanks are due to Judy Broughton for her comments on the Diabetes Knowledge Questionnaire and to Don Diner for his help with data analysis. Special appreciation is also extended to Michael A. Brownlee for his advice throughout this project and to the participating patients who made the study possible.
Quantitative electron microscopic studies of muscle capillary basement membrane are reported on 154 control subjects and 151 diabetics. In normal subjects and in diabetics significant thickening of basement membrane is observed as an aging phenomenon in both sexes. Significant age-related sex differences in basement membrane width are evident in normal subjects but not in diabetics. Observations on diabetics suggest that basement membrane width is probably normal in most subjects prior to the onset of carbohydrate intolerance and demonstrate that both the magnitude and incidence of basement membrane thickening increase with longer known duration of carbohydrate intolerance. Basement membrane thickening is demonstrable in a significantly higher percentage of subjects over age fifty (63 per cent) than in subjects under age fifty (25 per cent) who have had the disease for four years' known duration or less. The incidence increases to 90 per cent in subjects with complications of retinopathy and/ or nephropathy and to 93 per cent in subjects who have had known disease for twenty years or longer.Both morphologic and statistical evidence indicate that thickening of basement membranes related to aging and to diabetes is essentially segmental in character. DIABETES 21: 881-905, August, 1972. The relationship between known duration of diabetes and the incidence of retinopathy and nephropathy is, of course, well documented.
The primary aim of these experiments was to assess in vitro effects of hyperglycemia (30 mmol/l glucose) and hypoxia (PO 2 ؍ 36 torr) of 2-h duration, separately and in combination, on cytosolic and mitochondrial free NADH (NADHc and NADHm, respectively) in retinas from normal rats. NADH is the major carrier of electrons and protons that fuel ATP synthesis and several metabolic pathways linked to diabetic complications. T he importance of duration and severity of hyperglycemia in the development of diabetic retinopathy was clearly established by the Diabetes Control and Complications Trial (1); however, the mechanisms that mediate early and late retinal vascular dysfunction and structural changes remain unclear.Proliferative retinopathy is widely attributed to increased production of vascular endothelial growth factor evoked by hypoxia/ischemia caused by capillary closure and nonperfusion that develop relatively early after the onset of diabetes (2).The possibility that hyperglycemia and hypoxia may interact via a common metabolic imbalance(s) to initiate and/or exacerbate complications of diabetes is suggested by the correspondence of several redox, metabolic, and pathophysiological changes evoked by either condition alone. Examples include an increased ratio of reduced to oxidized free cytosolic NADc (3-16), increased production of free radicals (3,17-24) and vascular endothelial growth factor (17,19,(25)(26)(27)(28), accumulation of triose phosphates (7,9,10,13-15), activation of protein kinase C (PKC) (22,28 -30), decreased Na ϩ /K ϩ -ATPase activity (3,30 -33), early increases in blood flow (3,(33)(34)(35), and paradoxical protective effects of diabetes and brief periods of hypoxia/ ischemia (i.e., ischemic preconditioning) that attenuate dysfunction/injury evoked by subsequent more severe hypoxia/ischemia (3,29,36 -38).An increase in free NADH/NAD ϩ c appears to be the best candidate metabolic imbalance for mediating pathophysiological changes common to diabetes and hypoxia (3,38). This redox imbalance develops when electrons and protons are transferred to free oxidized NAD ϩ c (reducing it to NADHc) faster than electrons and protons carried by NADHc are used for ATP synthesis in mitochondria by oxidative phosphorylation. Hypoxia increases free NADHc because lack of O 2 impairs utilization of electrons and protons carried by mitochondrial NADHm for oxidative phosphorylation. The mass action effect of electrons and protons accumulating in NADHm restrains transfer of electrons and protons from free NADHc to NAD ϩ m by the malate-aspartate electron shuttle; thus, electrons and protons accumulate in, and elevate, free NADHc.In cells for which glucose uptake is insulin-independent, hyperglycemia augments glucose uptake and metabolism via the sorbitol pathway. In the second step of the pathway, sorbitol is oxidized to fructose by sorbitol dehydrogenase, which catalyzes transfer of a hydride ion (:H Ϫ ) from sorbitol to free NAD ϩ c (reducing it to NADHc) and removal of a second hydrogen atom that is released i...
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