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At least 19 recordsLinked to original sources
PubMedDate not supplied

[Microvascular complications in diabetes mellitus. Pathogenetic aspects].

Chronic microvascular complications are important causes of mortality and morbidity in people with diabetes mellitus. After 10 years of disease, nearly 70% of diabetics are affected by retinopathy and about 40% by nephropathy. Genetic factors have a great influence on the development of diabetic microvascular complications, as pointed out by their association with HLA system and Na/Li countertransport, but epidemiological and experimental studies show that the greater role is played by the metabolic milieu. Protein glycation, sorbitol pathway and lipid abnormalities can be responsible for early and fast development of the microvascular complications of diabetes mellitus.

Animals↗
PubMed1992

[Incidence and clinical expressions of microvascular complications in patients receiving kidney graft and treated with cyclosporine].

Reported cases of HUS/TTP (hemolytic uremic syndrome/thrombotic thrombopenic purpura) with cyclosporin (CsA) are more and more frequent, which led us to evaluate the incidence of microangiopathic process in kidney graft patients. In our first retrospective study we noted 9.4 percent of HUS/TTP among 117 patients. We tried to detect infraclinical hemolytic events prospectively in 40 new patients by systematic measurement of haptoglobin levels after introduction of CsA. The incidence of falls in haptoglobin levels was 25 percent. The immunological context was always noted: rejection crisis in 5 cases, cytomegalovirus infection in 3 cases, isolated markers of lymphocyte-activity in 2 cases. We never found a clinical or infraclinical form of microangiopathic process without a symptomatic or asymptomatic immunological complication. Monitoring haptoglobin levels make it possible to detect early endothelial injuries which could be linked to the future arteriolopathy described with CsA therapy.

Cyclosporine↗
PubMed1992

Incidence and clinical profile of microvascular complications in renal allografted patients treated with cyclosporine.

The incidence of cyclosporine (CsA) vascular toxicity is open to debate. We attempted to evaluate the incidence of hemolytic accidents in our series of patients taking all clinical forms into consideration. From January, 1989, to December, 1990, 117 patients received kidneys from cadaver donors and were treated with CsA. Five patients presented hemolytic uremic syndrome (HUS) accompanied by a rejection crisis; 6 patients presented hemolytic anemia associated in 2 cases with marked thrombocytopenia without any evidence of rejection. Cytomegalovirus (CMV) infection was diagnosed in 2 patients and bacterial infection preceded hemolysis in 2 other cases, suggesting a triggering factor. In addition, when we systematically determined haptoglobin levels after introduction of CsA treatment, we found asymptomatic hemolytic episodes more frequently. Our incidence of hemolytic accidents was approximately 10%. Hemolysis could indicate ischemic vascular damage leading to arteriolar medial hyalinosis preceding fibrosis in CsA nephrotoxicity. Thus, it would be interesting to detect asymptomatic forms of hemolysis by monitoring haptoglobin levels. This approach could lead to a reduction of the CsA dose in patients presenting low haptoglobin levels, even in the absence of evidence of nephrotoxicity.

Adult↗
PubMed1977

Experimental and clinical therapy of diabetes by transplantation.

Prevention, delay, or reversal of the microvascular complications of diabetes is the ultimate goal of pancreatic islet cell transplantation. Advances in surgical techniques and in islet isolation procedures have made the achievement of this goal a practical possibility. Microvascular lesions have indeed been prevented and even reversed in successful islet cell transplantation experiments in rats. Successful application of pancreatic islet cell transplantation in the human now awaits the development of effective suppression of rejection.

Animals↗
PubMed1992

Effective treatment of hypertension in patients with diabetes mellitus.

Atherosclerosis, presenting as macrovascular complications of diabetes mellitus, produces approximately 80% of all diabetic mortality, whether the patient has Type I insulin-dependent diabetes (IDDM) or Type II non-insulin dependent diabetes mellitus (NIDDM). Specifically, 75% of this atherosclerotic macrovascular mortality flows as the outcome of coronary atherosclerosis, which is increased approximately two-fold in men and four-fold in women with diabetes as compared with otherwise matched populations with entirely normal carbohydrate tolerance. The remaining 25% of this atherosclerotic mortality in patients with diabetes mellitus is the result either of accelerated cerebrovascular or of peripheral vascular complications of diabetes, both of which are increased four-fold and five-fold, respectively, in patients with diabetes mellitus, regardless of type. Furthermore, atherosclerosis is the principal cause of hospitalizations for patients with diabetes mellitus. Admissions for this complication account for approximately 77% of total hospitalizations for diabetes owing to complications. Aside from mortality data alone, atherosclerosis is obviously a leading cause of diabetic disability, since it produces patients who are chronic cardiovascular, peripheral or cerebrovascular cripples, perhaps for many years before their ultimate demise. Small blood vessel or microvascular complications of diabetes mellitus, while formerly thought to be the end-stage in the unfolding of the diabetic process, do not appear to have the potential for mortality as do the atherosclerotic large blood vessel complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Prevalence of major vascular complications at the initial visit among Japanese diabetic patients.

The frequencies of retinopathy, proteinuria, hypertension, and electrocardiographic (ECG) abnormalities in 2025 diabetic subjects new to our clinic in Tokyo were analyzed in relation to status at initial visit with respect to age, estimated duration of diabetes, and fasting blood glucose. Frequency and severity of retinopathy increased markedly with duration of diabetes. A relationship was found between retinopathy at first visit and level of blood glucose at that time. Proteinuria also clearly increased with duration; its frequency was generally higher in older age groups. Frequency of hypertension increased with age up to 60 yr, but there was no association between prevalence of hypertension and duration of diabetes. ECG abnormalities also increased with age, although serious abnormalities were rare even in older subjects. Hypertension and ECG abnormalities were not more common in those with higher initial blood glucose values, and the frequencies of these aberrations did not increase with the duration of diabetes. ECG abnormalities were more common among hypertensives, especially in younger age groups. Despite the clear effect of degree and duration of hyperglycemia on microvascular complications, there was no evidence of a direct effect of hyperglycemia on macrovascular abnormalities in this study.

Adult↗
PubMed1979

Oral glucose-tolerance tests and the diagnosis of diabetes: results of a prospective study based on the Whitehall survey.

Men who participated in the Whitehall survey and were found to be glucose intolerant have been studied 6--8 years later, together with a control group of men with normal screening blood-sugar levels. Ophthalmoscopically visible microvascular retinal disease was confined to men diagnosed as probably diabetic after the survey because their 2 h blood-sugar level (after a 50 g oral glucose load) in the survey examination or during a subsequent standard oral glucose-tolerance test was greater than or equal to 200 mg/dl (11.1 mmol/l). The lowest blood-sugar in a "diabetic" subsequently found to have retinopathy was 229 mg/dl. Men with lesser degrees of glucose intolerance, including 34 who had "worsened to diabetes", did not have visible retinovascular disease at follow-up. If diabetes implies a risk of specific microvascular complications in the medium term, then the findings in this study support proposals for the revision of diagnostic criteria based on glucose-tolerance tests.

Aged↗
PubMed1992

Inhibition by salbutamol of GHRH-induced GH release in type 1 diabetes mellitus.

Patients with type 1 diabetes mellitus (IDDM) show augmented GH secretion, which is implicated in the pathogenesis of microvascular complications. On the other hand, it is well known that beta-adrenergic receptors have inhibitory influence on GH secretion, likely via stimulation of hypothalamic somatostatin. Since the possibility of pharmacological suppression of GH secretion would be of value in IDDM, we investigated the effect of salbutamol (SAL, 4 mg orally at -60 min) on the GH response to GHRH (1 micrograms/kg iv at 0 min) in 6 well-controlled (mean HbA1c +/- SEM: 7.3 +/- 0.5%) patients with IDDM. Salbutamol was able to inhibit basal GH levels (p < 0.05) as well as to abolish the GHRH-induced GH rise. After SAL administration, a significant (p < 0.05) reduction of glucagon levels was also found. Our data show that the enhancement of beta 2 adrenergic activity by oral therapeutical doses of SAL inhibits basal and GHRH-stimulated GH secretion in patients with IDDM.

Adult↗
PubMed1979

Immune complexes in diabetes mellitus.

Sera from 86 well controlled diabetics were examined for the presence of immune complexes. Thirty-six patients were receiving standard insulins, 19 monocomponent preparations, 24 oral hypoglycaemic agents and seven dietary restriction alone. Three methods were used to detect complexes: measurement of complement components, a Clq binding assay (BA) and the Raji cell radioimmunoassay (RIA). Complement components were normal in all patients. Eleven (31%) of the group on standard insulins had a positive Raji cell RIA; none had an abnormal Clq-BA. One patient on monocomponent therapy had a mildly positive Raji cell RIA; Clq-BA was negative in each patient of this group. Thirteen (54%) of the patients on oral hypoglycaemic agents were positive on one or both assays while one patient on diet alone was abnormal on both assays. These data show that immune complex production is common in both insulin-requiring and non-insulin-requiring diabetics and that this phenomenon is strikingly less frequent in patients on monocomponent insulins. Such observations could bear relevance to the pathogenesis of microvascular complications in diabetes.

Adolescent↗
PubMed2025

Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring.

BACKGROUND: Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), represents the predominant cause of preventable vision loss in working-age populations globally. While the pathophysiological mechanisms underlying DR progression remain incompletely understood, our study employs comprehensive proteomic profiling of aqueous humor (AH) to identify stage-specific biomarkers and therapeutic targets in type 2 diabetes mellitus (T2DM) patients across DR progression. METHODS: Utilizing data-independent acquisition (DIA) mass spectrometry, we quantified AH proteomes in a discovery cohort comprising 24 subjects: 18 T2DM patients stratified by DR severity [6 non-DR, 6 non-proliferative DR (NPDR), 6 proliferative DR (PDR)] and 6 cataract controls without diabetes (non-DM). Validation cohort analysis (including 10 AH samples in each group) was performed using parallel reaction monitoring (PRM) strategy for verification of target proteins. Comprehensive bioinformatics analyses included gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network construction, receiver operating characteristic (ROC) curve analysis, and ConnectivityMap (Cmap)-based drug prediction. RESULTS: Proteomic profiling identified 739 quantifiable AH proteins (62% extracellular) with clear separation among the four clinical stages in the discovery cohort. GSEA uncovered altered expression of proteins mainly related to complement and coagulation cascades, folate metabolism, and the selenium micronutrient network in patients with DR. WGCNA-derived protein modules yielded 83 PRM-validated targets, including 5 hub proteins differentiating NPDR from non-DR and 33 hub proteins showed significant upregulation in PDR versus NPDR comparison. Clinical correlation analysis identified F2, FGG, FGB, RBP4, AMBP, VTN, C8A, CPB2, and C2 associated with clinical traits. C6, FAM3C, SPP1, and JCHAIN levels were altered post-anti-VEGF treatment. Pharmacological prediction identified potential therapeutic compounds, including perindopril, triciribine, and XAV-939 for NPDR, and topiramate, triciribine, and vecuronium for PDR. CONCLUSION: This study established a comprehensive AH proteomic signature of DR progression, offering insights into the pathogenesis of DR and highlighting potential biomarkers and novel therapeutic targets.

Humans↗
PubMed1977

Diabetic vascular changes in children.

The microvascular complications of diabetes are demonstrated in the eye at a very early stage with the use of retinal fluorescein angiography. One hundred and fifty-four children who have had diabetes mellitus for durations varying from one month to 18 years had their retinal vasculature evaluated with fluorescein angiography. Seventy-five per cent of the children examined had vascular abnormalities, including 20 children who had diabetes for one year or less. Twenty-five per cent of the children showed no vascular abnormalities. This included one child who had diabetes for 12 years. The severity of the vascular abnormalities increased with the duration of diabetes. Vascular abnormalities did not appear related to diabetic management or control. The possibility of two types of diabetics, one with the other without associated vascular abnormalities, is suggested.

Adolescent↗
PubMed1977

Relationship of microvascular disease in diabetes to metabolic control.

Dogs were made alloxan-diabetic and randomly distributed into either of two prospective treatment groups. In one group it was intended that the metabolic signs of diabetes be controlled poorly, and commercial insulin was administered in doses inadequate to prevent chronic, severe hyperglycemia and glucosuria. In the other group it was intended that the metabolic disorder be well controlled, and the animals received food and commercial insulin twice daily such that the hyperglycemia and glucosuria became mild or infrequent. Experimental improvement of the carbohydrate disorder was accompanied by amelioration of hyperlipemia and other clinical signs of deficient insulin activity. By 60 months of diabetes, retinal capillary aneurysms, pericyte ghosts, obliterated vessels, and other microvascular abnormalities typical of diabetes were apparent in each animal of the poor-control group. Better control was found to reduce significantly the incidence and severity of microvascular lesions. The data suggest that the mechanism responsible for diabetic retinopathy is initiated as a result of deficient insulin activity and that the development of the microvascular complications of diabetes are preventable and may be inhibited by careful control of the metabolic disorder.

Animals↗
PubMed1992

Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients.

Treatment with thiazide diuretics causes impaired glucose tolerance, biochemical diabetes, and insulin resistance. The effect of diuretics on glucose tolerance is clearly dose-related. Spironolactone does not impair glucose tolerance, even at high dosage, but differences among other diuretics could be due to comparisons at doses that are not equal. Diuretic-induced changes in glucose metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs even when relatively low doses of thiazide are combined with potassium-sparing agents. The effects of diuretics on glucose homeostasis are in large part and probably entirely reversible. These disturbances of glucose metabolism have been detected only by detailed biochemical testing, and their clinical relevance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In nondiabetic subjects, diuretics rarely cause or trigger a serious hyperosmolar nonketotic diabetic syndrome. Otherwise, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long term. Evidence from large outcome trials suggests that biochemical diabetes, glucose intolerance, and insulin resistance do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes unless their use is essential. Otherwise, a low dose of thiazide remains as excellent choice for first-line antihypertensive therapy. Dihydropyridine calcium antagonists, diltiazem, and verapamil appear to have no important effects on glucose homeostasis. There is very limited evidence that selective alpha-antagonists increase insulin sensitivity. The importance of metabolic differences between drug classes will be established only by comparative outcome trials with coronary events as the end point.

Adrenergic beta-Antagonists↗
PubMed1992

Rheological leukocyte indexes in diabetes mellitus type II.

Eleven healthy volunteers were examined, as well a thirty-five diabetic subjects divided into three groups according to the presence or absence of macro-microvascular complications and according to whether or not these complications were chronic. The results of our study show a marked unfavorable in cell rheology in the diabetic subjects, as studied using the St. George filtrometer. In particular, polymorphonuclear (PMN) cells, in the diabetic subject showed a substantial decreases in viscosity and elasticity, reflected by decreased IrFr and increased CR values. These changes were most marked in the group of diabetics with acute vascular events, i.e., AMI and stroke. Rheological indexes studied appeared to be independent from the simultaneous blood glucose level.

Aged↗
PubMed1992

Plasma prorenin as an early marker of microvascular disease in patients with diabetes mellitus.

To test the hypothesis that a high plasma prorenin can be used as an early marker of microvascular complications in patients with diabetes mellitus plasma prorenin was measured in 44 patients with urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) and 120 patients with urinary albumin excretion below 30 mg/24 h (normoalbuminuria). A high plasma prorenin was associated with diabetic retinopathy, particularly the proliferative type, serum creatinine and the 24 h urinary albumin excretion rate. Plasma prorenin was not correlated with age, duration of diabetes, glycosylated hemoglobin, blood glucose, and blood pressure. The association between elevated plasma prorenin and retinopathy remained significant after adjustment for serum creatinine and albumin excretion. Independent of the presence or absence of microalbuminuria, the mean plasma level of prorenin was not above normal in patients without retinopathy and was 2 to 3 times normal in patients with proliferative retinopathy. Thus retinopathy appears to be an important determinant of abnormally high plasma prorenin. Angiotensin converting enzyme (ACE) was elevated in the patients with diabetes mellitus as compared to control subjects but the plasma levels of ACE in diabetics with normoalbuminuria was not significantly different from the group with microalbuminuria. Plasma prorenin was not associated with ACE. A plasma level of prorenin of 225 mU/L had a sensitivity of 0.84 and a specificity of 0.82 for detecting the presence of microalbuminuria.

Adult↗
PubMed1992

Left ventricular diastolic filling in type I diabetes mellitus: a pulsed Doppler echocardiographic study.

OBJECTIVES: Doppler echocardiography was used to assess left ventricular diastolic performance in young patients with type I diabetes mellitus and no clinical signs of heart disease. METHODS: The pattern of transmitral diastolic flow velocity was determined in 82 patients (56 men, 26 women; age 17.7 +/- 7.6) with type I diabetes mellitus and no heart disease. Maximal early diastolic flow velocity (E peak), maximal late diastolic velocity (A peak), the ratio of maximal flow velocity in late diastole to that in early diastole (A/E ratio) and the ratio of the time velocity integral of the diastole (1/3 FF) were measured in all 82 patients and repeated during exercise in 63 of them. Twenty healthy volunteers served as controls. RESULTS: Mean values of the Doppler indexes were not significantly different between the patients and the 20 controls, but diabetic patients with microvascular complications showed patterns of left ventricular diastolic flow velocity which suggested altered diastolic performance, namely lower E peak velocity, higher A peak velocity, raised A/E ratio and reduced 1/3 FF. Among the 63 examined during exercise, different diastolic flow patterns in response to effort made it possible to identify 15 patients with a high rate of autonomic dysfunction, indicating probable impairment of diastolic function and a need for close follow-up. CONCLUSION: Diastolic abnormalities may occur in young diabetic patients without evidence of heart disease and suggest Doppler evaluation is a sensitive method for identifying patients at potential risk of developing clinical heart disease.

Adolescent↗