Relation of diabetic control to development of microvascular complications.
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Animals↗
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Recommendations on the standardization of methods and reporting of tests for diabetes and its microvascular complications in epidemiologic studies.
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Diabetes Mellitus↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Diabetes mellitus in pregnancy.
Physiologic changes that occur during pregnancy are diabetogenic. If diabetes does not exist before pregnancy, it may become evident, and if diabetes pre-exists, it becomes aggravated. The changing insulin requirements and propensity for ketoacidosis require weekly visits and careful urine testing on a daily basis by the mother. In addition, microvascular complications of diabetes must be carefully monitored. Delivery is planned progressively early in the pregnancy according to diabetic class. Hospitalization is necessary one week before anticipated delivery. Urinary estriol tests, OCT, amniocentesis, and ultrasound are all helpful in managing the pregnancy. Delivery of the fetus and placenta results in a profound fall in the insulin requirement. The neonate should be carefully observed during the first few days of life because of the increased frequency of complications.
Delivery, Obstetric↗
Integrative oral and gut microbiome profiling highlights microbial correlates of complications in type 1 diabetes: a cross-sectional analysis.
BACKGROUND/OBJECTIVE: Chronic vascular complications are the primary threat in long-standing type 1 diabetes (T1D) patients. We examined the associations between oral-gut microbiome dysbiosis and these complications, offering novel insights into therapeutic strategies and underlying mechanisms. METHODS: This cross-sectional study enrolled 75 T1D participants (disease duration ≥ 10 years) and 43 healthy controls who underwent comprehensive clinical assessment, including blood glucose, lipid profile, and complication-related examinations. Fecal and oral rinse samples were collected for shotgun metagenomic sequencing. T1D participants were stratified by the presence of microvascular (retinopathy, nephropathy, or neuropathy) or macrovascular complications separately. Microbial differences across groups were assessed. RESULTS: Significant differences in oral and gut microbiota compositions were observed between T1D participants with and without complications (both microvascular and macrovascular). A core set of 26 gut and 8 oral microbial species was specifically associated with vascular complications. Butyrate-producing gut bacteria (Blautia wexlerae, Anaerobutyricum hallii, Roseburia inulinivorans, A. soehngenii) and specific oral Neisseria species were enriched in T1D without complications individuals, suggesting protective effects against complications. Mediation analysis indicated associations consistent with partial mediation between certain microbial species and the relationships of glycemic control or insulin resistance (HbA1c, glucose risk index, estimated glucose disposal rate) with complication risk. Moreover, potential oral-gut microbiome interconnections were implicated in complication development. Finally, classification models integrating both oral and gut microbial features significantly outperformed models based on either site alone in distinguishing T1D patients with complications. CONCLUSIONS: Distinct oral and gut microbiome features are associated with chronic vascular complications in T1D. These findings highlight the potential of microbiome-targeted strategies for understanding and preventing T1D-related complications.
Humans↗
[Complications in free flap transfer with microvascular anastomosis].
We used free flap transfers with microvascular anastomoses to cover defects on head, leg, foot and hand. In our experiences of 12 cases we got 2 total and 3 partial necroses of the transplants. The possible causes of the failures are discussed, and the results are compared with other reports. The significance of the method in hand surgery is demonstrated, comparing groin and dorsalis pedis flaps.
Adolescent↗
Epidemiology of diabetes and its macrovascular manifestations in Pacific populations: the medical effects of social progress.
Worldwide diabetes epidemiology studies have shown quite marked differences in diabetes prevalence rates between ethnic groups. This pattern holds true in the Pacific region and provides unique opportunities for comparative studies. Diabetes is rare in Melanesians, and also in Polynesians, Micronesians, and Australian Aboriginals who retain their traditional life-style. High prevalence rates of insulin-independent diabetes have been demonstrated in Polynesians, Micronesians, and Australian aboriginals who have adopted a Western life-style. Along with the Pima Indians, the Micronesian population of Nauru have the highest diabetes prevalence yet reported--40% of people aged 20 yr and over. As diabetes is rare in traditional living Polynesians and Micronesians, yet high in westernized populations of these ethnic groups, it appears these people may have a "diabetic genotype" that is unmasked by the change in life-style. Obesity, a high caloric Western diet, and reduced physical activity may be the major precipitating factors. Bimodality of glucose tolerance distributions has been demonstrated in both westernized Polynesians and Micronesians. The frequency distributions of both fasting and 2-h postload glucose levels allow separation of these populations into normal and hyperglycemic groups. The optimal cut-off levels between the two groups were a fasting plasma glucose congruent to 140 mg/dl and a 2-h level of congruent 20 mg/dl. These findings provide a valid basis for the diagnosis of diabetes mellitus to be based on the above levels. Only sparse information exists on the prevalence of microvascular and macrovascular complications of diabetes in these populations. However, there is clear evidence that they are occurring and they are similar in nature to the complications seen in Caucasian diabetic patients. Coronary artery disease is not yet a major problem in Pacific Islanders although most of the major risk factors are not present in urbanized communities. However, with increasing westernization, and given more time for the pathologic process of atheroma to develop, it can be expected that coronary artery disease will become a major cause of morbidity and mortality in Polynesians, Micronesians, and the Australian aboriginal.
Adult↗
Renin-angiotensin-aldosterone system in diabetes mellitus.
The renin-angiotensin-aldosterone system appears to function normally in uncomplicated diabetes mellitus. Alterations in this system, however, have been observed in several of the microvascular and electrolyte complications associated with this disease. Plasma renin activity (PRA) and aldosterone are decreased in diabetic with nephropathy and hypertension, in those with neuropathy including orthostatic hypotension, and in those with hypoaldosteronism. PRA is low in rats with uncontrolled, nonketotic diabetes, and pressor responsiveness to angiotension II is increased in patients with diabetic retinopathy. Potential mechanisms responsible for the decreased PRA include plasma volume expansion, hyalin destruction of the juxtaglomerular cells, defective synthesis of renin, and inadequate catecholamine stimulation of renin, and inadequant cathecholamine stimulation of renin release. In diabetic ketoacidosis, PRA and aldosterone are stimulated secondary to the associated dehydration with hypovolemia. This report reviews the current status of the function of the renin-angiotensin-aldosterone system in diabetes mellitus and proposes a possible role for the altered function of this system in the pathophysiology of several diabetic complications.
Aldosterone↗
[Failures and complications in vascular microsurgery].
Intraoperative and postoperative complications in the field of microvascular surgery are summarised. Some of them are discussed in detail (confusion of vessels, anastomosis under tension etc.), and precautions are outlined to avoid these complications. Failures can result from wrong indications, from incorrect technique of operation or from incorrect postoperative care.
Adult↗
Microvascular techniques for polar artery reconstruction in kidney transplants.
The complications of ureteral ischemia make revascularization of polar vessels attractive in cadaver and live-related transplants. Thirty-two patients underwent reconstruction of polar vessels of 1.2 to 2.5 mm, in diameter after revascularization of the major vessels as follows: (1) inferior epigastric artery to polar artery, ten patients - six cadaver transplants, four living-related transplants (The vessels are spatulated and sutured precisely by microvascular techniques with Nos. 7-0 or 8-0 Tevdek); (2) polar vessel with a patch of aorta to iliac artery, one patient - living relative donor; (3) polar artery to the main renal artery or branch, 17 patients - 14 cadaver transplants, three living-related transplants [A Waters "MOX"-100 machine is used with cryoprecipitated plasma (800 mg. of SoluMedrol and 80 U. of insulin added) for preservation.]; (4) autogenous saphenous vein graft, two patients - one child receiving on adult live-related kidney and one cadaver transplant with three arteries and a stenosis of the inferior polar vessel; (5) polar artery to vein patch in iliac artery, two patients - cadaver transplants. Follow-up was done by arteriography (18 patients), direct observation (two patients), and by use of ultrasound (one patient). The remaining 11 patients have exhibited no evidence of occlusion. Twenty of 21 patients exhibited patent vessels; one thrombosed at the time of the transplant operation. Long-term patency in those patients studied was 95%. We advocate small-vessel reconstruction in human renal transplantation, either during ex vivo preservation (workbench surgery) or at the time of transplantation.
Arteriovenous Shunt, Surgical↗
Cochlear Implantation in Sickle Cell Disease: A Systematic Review of Feasibility and Outcomes.
INTRODUCTION: Sickle cell disease (SCD) is associated with systemic complications, including sensorineural hearing loss (SNHL) from microvascular occlusion and chronic inflammation. Although reports link SCD to higher rates of SNHL, current evidence is limited by small sample size, varied audiologic methods, and lack of standardized screening. This systematic review summarizes available literature on SNHL and cochlear implantation (CI) in SCD. METHODS: A literature search of PubMed MEDLINE, Embase, Scopus, Web of Science, and CINAHL identified 79 citations. After removal of duplicates, 35 records were screened in Rayyan. Studies published between January 1, 2000, and June 30, 2025, were eligible if they reported patients with SCD who developed hearing loss and underwent CI. Nine full texts were reviewed, and 4 met the inclusion criteria. Screening and review were performed independently by 2 authors per PRISMA guidelines. RESULTS: Across 4 case reports, a total of 5 patients with SCD underwent CI, ranging in age from 2 to 42 years. Four presented with bilateral severe-to-profound SNHL and one with unilateral loss. Implantation was technically feasible in all cases, including patients with cochlear fibrosis or ossification requiring modified insertion techniques. Postoperative outcomes were favorable: all patients demonstrated reliable device function and low impedances. Only 60% showed meaningful auditory benefit, characterized by improved functional speech perception in 2 patients (40%) and access to the speech frequency range with hearing testing going from moderate/profound hearing loss to mild hearing loss in 3 patients (60%). Complications occurred in 2 patients (40%): one developed unilateral middle ear infection leading to meningitis, and another experienced a postoperative pulmonary embolism requiring anticoagulation. The remaining 3 patients (60%) had uncomplicated recoveries with reported improved hearing from moderate/profound hearing loss to mild hearing loss post implantation. CONCLUSION: While CI appears feasible in SCD, our findings suggest that additional data are needed to assess its effectiveness in this patient population. However, evidence is limited to case reports, and complications such as thromboembolism and rapid cochlear fibrosis highlight the need for close perioperative management. More comprehensive studies with larger sample size are required to define surgical risk, optimize management, and establish best practices for timely implantation in this population.
Humans↗
Genetic predisposition and mediating pathways in ischemic stroke-induced cardiac arrhythmias: a genome-wide analysis.
INTRODUCTION: The clinical presentation of stroke-heart syndrome (SHS) underscores the interplay between the central nervous system and the cardiovascular system. While cardiac arrhythmia is the prevalent form of cardiac injury in SHS patients, the causal link between ischemic stroke and cardiac arrhythmia is still unclear. METHODS: Mendelian randomization analyses and genome-wide association studies data were used to investigate the causal role of ischemic stroke on cardiac complications. Mediation and colocalization analyses were used to identify potential pathways and shared genetic variants. Single nucleotide polymorphisms (SNPs) associated with arrhythmias and ischemic stroke were used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Gene expression omnibus (GEO) database from atrial fibrillation patients were used for validation. RESULTS: Mendelian randomization analyses showed a strong correlation between arrhythmias, including ventricular tachyarrhythmias and atrial fibrillation, with ischemic stroke. Diabetic microvascular (nephropathy, retinopathy) and macrovascular (cardiomyopathy, peripheral arterial disease) complications significantly mediated the effect of ischemic stroke on cardiac arrhythmias and atrial fibrillation, explaining 28.69 % and 20.48 % of the indirect effect, respectively. Colocalization analyses identified a shared causal variant in the Phosphodiesterase 3A (PDE3A) gene (rs11045239), providing genetic evidence for a shared pathogenic pathway between ischemic stroke and cardiac arrhythmias. Moreover, KEGG pathway enrichment analyses identified a role of the cyclic adenosine monophosphate (cAMP) signaling pathway in both ischemic stroke and arrhythmias. Validation using the GEO database confirmed a significant upregulation of the PDE3A gene expression in atrial fibrillation patients. CONCLUSION: This study demonstrated a causal link between ischemic stroke and cardiac arrhythmias, with diabetic complications as one mediating factor. The identification of a shared causal variant in the PDE3A gene and the role of the cAMP signaling pathway have the potential to improve prediction and management of SHS patients.
Humans↗