Macrovascular Changes Research Articles

Is scleroderma a vasculopathy?

Described as an autoimmune collagen vascular disease, the most striking feature of scleroderma may be a systemic vasculopathy. This vasculopathy includes characteristic noninflammatory macrovascular and microvascular changes with dramatic and possibly occlusive formation of a thickened neointima. Scleroderma vessels also have an unusual endothelial phenotype, with loss of normal markers including vascular endothelial (VE)-cadherin. These endothelial cells express type 1 interferon and regulator of G protein signaling 5 (RGS5), two molecules associated with vascular rarefaction. These genes may be important because tissue is hypoxic with high levels of vascular endothelial growth factor (VEGF), especially early in the disease. The combination of VEGF and rarefaction is not necessarily paradoxical. VEGF-mediated angiogenesis creates labile vessels that may not survive unless the vessel acquires a smooth muscle coat. The combination of interferon and RGS5 is consistent with an antiangiogenic phenotype. We offer a hypothesis that places vascular injury at the center of this disease and also suggest possible clinical approaches for arresting and/or reversing the disease.

Periodontitis and diabetes: a challenge for interdisciplinary teams

BACKGROUND: Diabetes is a widespread disease in adults and children with a tremendous impact on every diseased person. The risk of co-morbidities such as retinopathy, nephropathy, neuropathy, coronary and peripheral vascular diseases and cerebrovascular events is dramatically increased compared to non-diabetic persons. Micro- and macrovascular changes are pathogenetic mechanism by which the impaired glycaemic control causes acute and chronic complications. Chronic infections such as Periodontitis and Gingivitis have been identified as risk factors in the development of diabetes. Due to this chronic infection, the systemic inflammatory metabolism is raised and contributes to the unfavourable pathomechanism. PURPOSE OF THE REVIEW: This review identifies the relationship of periodontal disease and diabetes mellitus. The burden of diabetes today and in the future, based on the prognosis of WHO data, illustrates the immense impact on health and social systems worldwide, not only in developing, but also in developed countries. RESULTS: Diagnosis at an early stage and adequate therapeutical strategies are essential tools in the contemporary management of diabetic patients. Control of chronic infections such as Gingivitis and Periodontitis seems to be a cornerstone in an up-to-date therapeutical concept. An interdisciplinary team approach is essential, based on the profound knowledge of the mechanism of periodontal medicine. CONCLUSION: Future interdisciplinary research has to be conducted to clarify the following questions: • Is oral hygiene effective in terms of preventing untoward adverse effects in diabetic patients? • Is there a possibility to prevent children with imbalanced glycaemic control from developing diabetes by controlling intraoral infection? • Are dentists and dental hygienists able to communicate the evident need of controlling intraoral infection to prevent adverse events and co-morbidities in diabetic patients? • Are there possible dental pre-screening methods for patients with undiagnosed or uncontrolled diabetes? • What is the best interdisciplinary approach for communicating intraoral findings with other specialists such as endocrinologist and paediatricians?

Diabetes mellitus and cognition: is there a link?

The occurrence of diabetes and dementia is very high in older patients. The fact that both conditions are concurrent raises the question of a possible link between the two. Cognitive functions of non-demented patients with diabetes have been extensively studied. In type 1 diabetes, only a mild decrease of the speed of information processing and of the psychomotor efficiency has been shown. Cognitive decline seems to be related to poor metabolic control and not to hypoglycaemia. In older patients with type 2 diabetes, memory and executive functions have been found impaired. Longitudinal studies of the literature have shown that diabetic patients have a higher chance of developing dementia than non-diabetic patient, with a relative risk (RR) between 1.26 and 2.83. The risk of vascular dementia was increased in 3 out of 5 studies, with a RR ranging between 2 and 2.6. With regard to Alzheimer's disease, the results are conflicting. Half of the studies found an increased risk in diabetic patients (RR: 1.3-2). The possible causal mechanisms of dementia in diabetic patients remain hypothetical. MRI studies showed varying degrees of cortical atrophy, cerebral infarcts and deep white matter lesions. In neuropathological studies, senile plaques and neurofibrillary tangle were not found with higher severity in the brain of diabetic patients than in the brain of age-matched controls. Several hypotheses have been raised to explain the relationship between diabetes and cognitive decline. Micro and macrovascular changes in the brain could induce cerebral hypoxia and ischemic conditions resulting in cellular death or white matter lesions. The occurrence of vascular lesions might reduce the threshold at which dementia will occur in Alzheimer disease. The deposition of advanced glycation end products doesn't spare the brain and they have been found in senile plaques, where they can reduce the solubility of proteins such as the beta amyloid and Tau proteins. Some authors favour the hypothesis of a brain insulin resistance because, in a few small studies, insulin was found to improve memory.

From macro- to microcirculation: benefits in hypertension and diabetes

Chronic hypertension and diabetes produce both macrovascular and microvascular pathophysiological changes. Greater arterial stiffness increases central systolic and pulse pressure, which raises left ventricular afterload and reduces coronary perfusion. Resistance arteries remodelling and capillary rarefaction increase peripheral resistance, thereby contributing to hypertension and amplifying the detrimental haemodynamic effects of arterial stiffening. The result is target organ impairment, such as left ventricular hypertrophy, decreased coronary perfusion pressure, reduced coronary reserve and further vascular remodelling, culminating in coronary artery disease and stroke. Therapeutic intervention is possible and necessary to stop these vascular changes. Vasodilating antihypertensive drugs, such as the perindopril/indapamide combination, have been shown to modify both arterial and arteriolar remodelling, leading to reduced central systolic blood pressure and enhancing vascular bed perfusion. These effects probably underpin the benefits of these agents in reducing cardiovascular morbidity and mortality.

Proximal Cerebral Artery Stenosis in a Patient with Hemolytic Uremic Syndrome: Fig 1.

Neurologic complications occur in 20%–50% of patients with hemolytic uremic syndrome (HUS). Macrovascular changes are not part of the syndrome. Here, we report a patient with a familial form of HUS who presented with hemodynamic transient ischemic attacks, as a result of severe proximal stenoses

The association of early atherosclerosis and retinopathy in adolescents with type 1 diabetes: preliminary report

Recent studies have shown a close correlation between advanced diabetic retinopathy and the late stages of atherosclerosis. The purpose of this study was to analyse the association between diabetic retinopathy and early atherosclerotic changes in adolescents with type 1 diabetes. We studied 28 adolescents with type 1 diabetes. Eight patients with nonproliferative retinopathy were compared with the remaining 20 patients, and with 11 healthy controls. The function of endothelium was assessed by measuring flow-mediated dilatation (FMD), the intima-media thickness (IMT) of the common carotid arteries and adhesion molecules (sICAM-1, sVCAM-1, sE-selectin). In the group with retinopathy FMD equalled 7.8+/-4.1% vs. 12.1+/-5.1% in the control group (p=0.04), and in the group without retinopathy, 7.6+/-5.5% (p=0.04 compared to controls). Higher IMT was found in all patients with diabetes in comparison with healthy controls: 0.49+/-0.06 mm vs. 0.42+/-0.03 mm (p=0.001). Patients with retinopathy had a significantly higher value of IMT in comparison not only with controls but also with patients without complications: 0.56+/-0.06 mm vs. 0.47+/-0.03 mm (p=0.0001). Adhesion molecule levels were not changed in patients with retinopathy. Higher IMT was found in adolescents with diabetic retinopathy in comparison with patients without complications, which may suggest that macrovascular changes are more advanced in these patients than in their diabetic peers without retinopathy.

Gender Differences in the Treatment for Acute Myocardial Infarction

Accumulating evidence over the last several decades regarding the treatment and outcomes for coronary artery disease reveals disparities that have a clear relationship to gender. It had previously been thought that these differences were related to gender bias in physicians’ approach to treatment; thus, the term Yentl syndrome was coined in 1991.1 As the volume of literature expanded and clinical studies included more women, it became clear that outcomes after treatment for coronary artery disease, particularly acute myocardial infarction, were different for women compared with men. Women have a well-documented higher mortality after acute myocardial infarction.2 Much of this disparity has been attributed to differences in age and attendant comorbidities. Female patients with coronary artery disease typically are older, have a higher prevalence of risk factors, and have a lower functional status than their male counterparts.3,4 Additionally, women appear to be at higher risk than men when diabetes, hypertriglyceridemia, and metabolic syndrome are present. The underuse of revascularization procedures in women has been suggested as an explanation, but it has not been uniformly demonstrated to explain increases in mortality. Some studies have suggested a link to less aggressive hospital care of female patients, including the underuse of revascularization, as an explanation for their increased mortality.5 Other studies have indicated age and comorbidity as the primary factors leading to mortality differences.6 Still other studies suggest no evidence of undertreatment.7,8 Article p 833 Gender differences in the clinical outcome of patients with acute myocardial infarction may be explained in part by the female status. Several conditions found only in women hint at differences in the pathophysiology of ischemic vascular disease between the sexes. Such female-specific conditions include early menopause, gestational diabetes, peripartum vascular dissection, preeclampsia and eclampsia, polycystic ovarian syndrome, low-birth-weight children, and hypothalamic hypoestrogenemia. Several …

Diabetic Peripheral Neuropathic Pain: Clinical and Quality-of-Life Issues

Diabetic peripheral neuropathy (DPN) is estimated to be present in 50% of people living with diabetes mellitus (DM). Comorbidities of DM, such as macrovascular and microvascular changes, also Interact with DPN and affect its course. In patients with DM, DPN Is the leading cause of foot ulcers, which in turn are a major cause of amputation in the United States. Although most patients with DPN do not have pain, approximately 11% of patients with DPN have chronic, painful symptoms that diminish quality of life, disrupt sleep, and can lead to depression. Despite the number of patients affected by DPN pain, little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. This article reviews the current knowledge about and presents recommendations for diagnostic assessment of DPN pain based on a review of the literature.

Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy

In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2 (4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P< 0.001).

Arterial stiffness in Type 1 diabetes mellitus is aggravated by autoimmune thyroid disease

The aim of our study was to measure arterial stiffness in patients with Type 1 diabetes mellitus, its contributing factors and its relation to macrovascular arterial changes. Thirty-one female Type 1 diabetic patients were studied; 11 had concomitant autoimmune thyroid disease although euthyroid during the study period. Stiffness was studied using applanation tonometry and pulse wave analysis for evaluation of systolic arterial pressure augmentation secondary to arterial stiffening and early wave reflection. Results were compared to 24 healthy individuals. In all patients, endothelium-related flow-mediated dilation (FMD) of the brachial artery and intima-media thickness (IMT) of the carotid artery were measured. Augmentation pressure (AP) and augmentation index (AI) were higher in Type 1 diabetic patients suggesting stiffer arteries compared to controls (AP: 5.8 +/- 3.6 vs 2.8 +/- 2.2 mmHg, p < 0.001; and AI:18.3 +/- 9 vs 11.1 +/- 8.8%, p = 0.004). The subgroup of diabetic patients with autoimmune thyroid disease presented stiffer arteries than those without (AP: 6.5 +/- 2.9 vs 5.5 +/- 3.9 mmHg, p < 0.05; and AI: 21.3 +/- 5.4 vs 16.7 +/- 10.3%, p < 0.05), though the two groups did not differ statistically by means of age, disease duration, hemoglobin A1c (HbA1c), lipid levels, FMD and IMT. In multiple regression analysis, variables independently associated to AI in the diabetes group were: age (p = 0.028), IMT of the carotid artery bifurcation (p = 0.045), disease duration (p = 0.031) and autoimmune thyroid disease (p = 0.015). No correlation was observed between AI and metabolic control, blood pressure, microalbuminuria, presence of retinopathy and endothelial function (FMD). Women with Type 1 diabetes have increased arterial stiffness, which indicates macroangiopathy. An independent correlation between these indices and carotid IMT was observed. Concomitant autoimmune thyroid disease seems to aggravate arterial compliance in these patients, a finding that merits further investigation.

The Impact of Gender on Progression of Renal Disease: Potential Role of Estrogen-Mediated Vascular Endothelial Growth Factor Regulation and Vascular Protection

Male gender is associated with a more rapid progression of renal disease independent of blood pressure, dietary protein intake, or serum lipid levels. Recently, we reported a key role for the intrarenal vasculature in progressive renal disease (Kang D-H, Kanellis J, Hugo C, Truong L, Anderson S, Kerjaschki D, Schreiner GF, Johnson RJ: Role of endothelium in progressive renal disease. J Am Soc Nephrol 2002, 13:806-816). We hypothesized that estrogen-mediated preservation of the renal vasculature could account for the better renal outcome in female rats. We analyzed micro- and macrovascular changes in the 5/6 remnant kidney (RK) models both in male (n = 24) and female (n = 24) Sprague-Dawley rats up to 12 weeks after renal mass reduction. At 12 weeks, male and female RK rats had equivalent blood pressure, glomerular tuft area, and RK/body weight, but male rats showed worse renal function, proteinuria, glomerulosclerosis (%), and tubulointerstitial fibrosis. At 12 weeks peritubular capillary (PTC) EC proliferation and PTC density were higher in female RK rats whereas macrovascular changes in preglomerular vessels (smooth muscle cell proliferation, medial wall thickening, and adventitial fibrosis) were less prominent. The expression of vascular endothelial growth factor (VEGF) and VEGF type 2 receptor (flk-1) in renal cortex assessed by immunostaining were higher in female RK rats. To dissect the mechanism of sex hormone-induced vascular remodeling and VEGF regulation, we investigated the in vitro effect of 17 beta-estradiol (17 beta E, 10 nmol/L) on proliferation and VEGF expression of renal tubular cells (rat proximal tubular cells), vascular smooth muscle cells (VSMCs), and human umbilical vein endothelial cells (HUVECs). 17 beta E directly stimulated the proliferation of HUVECs, whereas it inhibited serum-induced proliferation of VSMCs. 17 beta E stimulated VEGF mRNA expression both in renal tubular cells and VSMCs. However, when cells were pretreated with a nitric oxide donor to simulate the in vivo condition, 17 beta E inhibited VEGF mRNA expression and protein release in VSMCs. In conclusion, female RK rats developed less glomerulosclerosis and renal failure compared to male RK rats in association with greater preservation of PTC and less preglomerular arteriopathy. Estrogen stimulated basal VEGF expression in renal tubular cells. We propose that estrogen may protect female rats in progressive renal disease by stimulating VEGF expression and maintaining a healthy intrarenal vasculature.

Intelligent data analysis to interpret major risk factors for diabetic patients with and without ischemic stroke in a small population.

This study proposes an intelligent data analysis approach to investigate and interpret the distinctive factors of diabetes mellitus patients with and without ischemic (non-embolic type) stroke in a small population. The database consists of a total of 16 features collected from 44 diabetic patients. Features include age, gender, duration of diabetes, cholesterol, high density lipoprotein, triglyceride levels, neuropathy, nephropathy, retinopathy, peripheral vascular disease, myocardial infarction rate, glucose level, medication and blood pressure. Metric and non-metric features are distinguished. First, the mean and covariance of the data are estimated and the correlated components are observed. Second, major components are extracted by principal component analysis. Finally, as common examples of local and global classification approach, a k-nearest neighbor and a high-degree polynomial classifier such as multilayer perceptron are employed for classification with all the components and major components case. Macrovascular changes emerged as the principal distinctive factors of ischemic-stroke in diabetes mellitus. Microvascular changes were generally ineffective discriminators. Recommendations were made according to the rules of evidence-based medicine. Briefly, this case study, based on a small population, supports theories of stroke in diabetes mellitus patients and also concludes that the use of intelligent data analysis improves personalized preventive intervention.

A Guideline for the Use of Pharmacoeconomic Models of Diabetes Treatment in the US Managed-Care Environment

The Academy of Managed Care Pharmacy has recently created guidelines for the submission of pharmacoeconomic models. Although these guidelines provide a general framework for the integration of pharmacoeconomic models in the drug selection process, a more disease-specific and practical 'hands-on' approach is needed for pharmacy staff and Pharmacy and Therapeutics (P&T) committee members. To answer the question, 'How can pharmacoeconomic models comparing treatments for diabetes and its complications be evaluated and used to make more informed formulary decisions?' We determined the information needs of a managed care organisation (MCO) making coverage decisions for diabetes therapies and reviewed current guidelines for the submission of pharmacoeconomic models to MCOs. We then developed a set of practical questions for evaluating models of diabetes treatment in a managed-care environment. Information needed by P&T committees in relation to new diabetes medications includes the long-term benefits of reduced micro- and macrovascular complications and changes in drug utilisation patterns, in addition to the immediate drug budget impact. Because diabetes is a complex disease, the peer-review process should be relied on as a first step to help ensure the validity of a model. Then, the end-user of a model should evaluate the sources of data to inform the model,the generalisability of the model for an MCO population, andthe face validity of the assumptions of the model. Pharmacoeconomic models in diabetes offer potential for assisting P&T committee members in making more informed decisions. The guidelines presented here provide a practical approach for model assessment. However, additional expertise will be needed by MCOs to appropriately evaluate these models, and joint educational programmes between managed care, academia, and industry should be considered as a mechanism for improving technology assessment in diabetes care.

Diagnosis Of Leg Ulcers

In the United States, leg ulcers present a significant clinical problem, occurring at a rate of approximately 600,000 new cases per year. (1) The most common types are venous, arterial, and neuropathic ulcers. Venous hypertension is the primary culprit in venous ulcerations. Peripheral vascular disease due to atherosclerosis with microvascular or macrovascular changes leads to ischemic ulcers. Sensory impairment with loss of protective sensation in the foot and repetitive trauma lead to neuropathic ulcers. Unusual causes of leg ulcers must be considered in the differential diagnosis. To arrive at the diagnosis, the clinician must perform a thorough history and physical examination, and order relevant investigative studies. Good management of chronic leg ulcers depends on correction of identified underlying conditions, long-term multidisciplinary care effort, and integrating traditional and new wound-healing technologies. Most patients with chronic leg ulcers benefit from the use of compression bandaging at a level appropriate to their vascular status. Venous ulcers must be managed with an arsenal of strategies to control venous insufficiency, heal the wound, and prevent recurrence. Surgery with revascularization remains the treatment of choice for chronic ischemic leg ulcers. In the absence of vascular compromise, up to 90 percent of neuropathic ulcers will heal with proper ulcer debridement, treatment of infection, saline wet-to-dry dressings, and relief of weight from the ulcerated area. The available armamentarium for wound care includes over 2000 wound dressing products and elastic compression wraps. Chronic leg ulcer treatment options have been expanded by alternatives available to treating these wounds. These alternatives include hyperbaric oxygen therapy, bioengineered skin substitutes, recombinant platelet-derived growth factors and vacuum assisted wound closure. Patients with large leg ulcers may benefit from skin grafting. Other patients may benefit from ligation and stripping of superficial veins or subfascial interruption of perforating veins.

Management Of Leg Ulcers

In the United States, leg ulcers present a significant clinical problem, occurring at a rate of approximately 600,000 new cases per year. (1) The most common types are venous, arterial, and neuropathic ulcers. Venous hypertension is the primary culprit in venous ulcerations. Peripheral vascular disease due to atherosclerosis with microvascular or macrovascular changes leads to ischemic ulcers. Sensory impairment with loss of protective sensation in the foot and repetitive trauma lead to neuropathic ulcers. Unusual causes of leg ulcers must be considered in the differential diagnosis. To arrive at the diagnosis, the clinician must perform a thorough history and physical examination, and order relevant investigative studies. Good management of chronic leg ulcers depends on correction of identified underlying conditions, long-term multidisciplinary care effort, and integrating traditional and new wound-healing technologies. Most patients with chronic leg ulcers benefit from the use of compression bandaging at a level appropriate to their vascular status. Venous ulcers must be managed with an arsenal of strategies to control venous insufficiency, heal the wound, and prevent recurrence. Surgery with revascularization remains the treatment of choice for chronic ischemic leg ulcers. In the absence of vascular compromise, up to 90 percent of neuropathic ulcers will heal with proper ulcer debridement, treatment of infection, saline wet-to-dry dressings, and relief of weight from the ulcerated area. The available armamentarium for wound care includes over 2000 wound dressing products and elastic compression wraps. Chronic leg ulcer treatment options have been expanded by alternatives available to treating these wounds. These alternatives include hyperbaric oxygen therapy, bioengineered skin substitutes, recombinant platelet-derived growth factors and vacuum assisted wound closure. Patients with large leg ulcers may benefit from skin grafting. Other patients may benefit from ligation and stripping of superficial veins or subfascial interruption of perforating veins.

Changes in microvascular fluid filtration capacity during 120 days of 6 degrees head-down tilt.

We used venous congestion strain gauge plethysmography (VCP) to measure the changes in fluid filtration capacity (K(f)), isovolumetric venous pressure (Pv(i)), and blood flow in six volunteers before, on the 118th day (D118) of head-down tilt (HDT), and 2 days after remobilization (Post). We hypothesized that 120 days of HDT cause significant micro- and macrovascular changes. We observed a significant increase in K(f) from 3.6 +/- 0.4 x 10(-3) to 5.7 +/- 0.9 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1) (+51.4%; P < 0.003), which returned to pretilt values (4.0 + 0.4 x 10(-3) ml. min(-1). 100 ml(-1). mmHg(-1)) after remobilization. Similarly, Pv(i) increased from 13.4 +/- 2.1 mmHg to 28.9 +/- 2.8 mmHg (+105.8%; P < 0.001) at D118 and was not significantly different at Post (12.4 +/- 2.6 mmHg). Blood flow decreased significantly from 2.3 +/- 0.3 to 1.3 +/- 0.2 ml. min(-1). 100 ml tissue(-1) at D118 and was found elevated to 3.4 +/- 0.7 ml. min(-1). 100 ml tissue(-1) at Post. We believe that the increased K(f) is caused by a higher microvascular water permeability. Because this may result in edema formation, it could contribute to the alterations in fluid homeostasis after exposure to microgravity.

Abstracts of literature

Abstracts of literature

Obesity induced by neonatal monosodium glutamate treatment in spontaneously hypertensive rats: an animal model of multiple risk factors.

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases.

Effects of long-term high-fiber diet on macrovascular changes and lipid and glucose levels in STZ-induced diabetic SD rats

The effects of long-term high-fiber diet on lipid and glucose levels and the histological changes in the coronary arteries and thoracic aorta in STZ-induced diabetic SD rats were investigated. During the first 4 weeks of the study period, all diabetic rats were given regular chow plus water after which, all were grouped according to the following diet regimen: group II, no added cholesterol and glucomannan; group III, no added cholesterol but with glucomannan supplement, group IV, with added cholesterol but no glucomannan supplement; and group V, with both cholesterol and glucomannan supplements. 15% weight of glucomannan and 1.5% weight of cholesterol in regular rat chow were used as supplements when indicated. Non-diabetic rats which received only regular chow served as the control group (group I). In the 18th week all rats were sacrificed and weight gain, glucose, total cholesterol, HDL-cholesterol, triglyceride and lipid peroxidase concentrations were determined. Selected portions of the heart and thoracic aorta were histologically examined. Weight gain was higher in rats supplemented with glucomannan than in those without glucomannan supplements, but the difference is not significant. A lowering tendency in glucose levels was likewise observed. Furthermore, total cholesterol and HDL-cholesterol levels were lower and higher, respectively in diabetic rats receiving glucomannan. Although the triglyceride levels were similar in all rats, lipid peroxidase levels were significantly lower in rats with high-fiber diet. Pathologic lesions of the coronary arteries and thoracic aorta consistent with atherosclerosis were found mostly in rats fed with added cholesterol but with no glucomannan supplement. These results suggest that high-fiber diet using glucomannan as a supplement confers beneficial effects on lipid and glucose levels and might help retard or prevent the formation of atherosclerosis in diabetes.

Etiology and Pathogenesis of Diabetes Mellitus

The concept that diabetes mellitus is not a single disease. but rather a clinical syndrome characterized by inappropriately elevated fasting or post-prandial blood glucoses and the development of long-term microvascular, macrovascular, and neuropathic changes is of very recent origin and stems from numerous investigations into the epidemiology, genetics, etiology, and pathogenesis of clinical diabetic states. This article reviews some of these data and indicates that the various forms of diabetes mellitus have markedly different etiologies and pathogenetic mechanisms and that these must be recognized in order to understand and care for patients.