One-Year Clinical Outcomes and Prognostic Factors Following Revascularization in Patients With Acute Limb Ischemia　- Results From the RESCUE ALI Study.

BACKGROUND: Acute limb ischemia (ALI) is a limb- and life-threatening condition and urgent treatment including revascularization should be offered to patients unless the limb is irreversibly ischemic. The aim of this study was to investigate 1-year clinical outcomes and prognostic factors following revascularization in patients with ALI.Methods and Results: A retrospective, multicenter, nonrandomized study examined 185 consecutive patients with ALI treated by surgical revascularization (SR), endovascular revascularization (ER), or hybrid revascularization (HR) in 6 Japanese medical centers from January 2015 to August 2021. The 1-year amputation-free survival (AFS) rate was estimated to be 69.2% (95% confidence interval [CI], 62.8-76.2%). There were no significant differences among SR, ER, and HR regarding both technical success and perioperative complications. Multivariate analysis revealed that Rutherford category IIb and III ischemia (hazard ratio [HR]: 1.86; 95% CI: 1.06-3.25), supra- to infrapopliteal lesion (HR: 2.06; 95% CI: 1.08-3.95), and technical failure (HR: 2.58; 95% CI: 1.49-4.46) were independent risk factors for 1-year AFS. CONCLUSIONS: Rutherford category IIb and III ischemia, supra- to infrapopliteal lesions, and technical failures were identified as independent risk factors for 1-year AFS. Furthermore, patients with multiple risk factors had a lower AFS rate.

Management of Acute Lower Limb Ischemia Without Surgical Revascularization - A Population-Based Study.

OBJECTIVES: To evaluate outcomes of management without surgical revascularization in patients with acute lower limb ischemia (ALI) in a population-based setting. DESIGN: Retrospective observational population-based study. MATERIALS: Patients from Malmö, Sweden, hospitalized for ALI between 2015 and 2018. METHODS: In-hospital, surgical, radiological, and autopsy registries were scrutinized for descriptive data on ALI patients managed by endovascular and open vascular surgery, conservative vascular therapy, primary major amputation, and palliative care. RESULTS: Among 161 patients, 73 (45.3%) did not undergo any operative revascularization. Conservative vascular therapy, primary amputation, and palliative care were conducted in 25 (15.5%), 26 (16.1%), and 22 (13.7%) patients, respectively. Conservatively treated patients had Rutherford class ≥ IIb ischemia and embolic occlusion in 33% and 68% of cases, respectively. Their median C-reactive protein level at admission was 7 mg/L (interquartile range 2 - 31 mg/L). Among conservatively treated patients, anticoagulation therapy in half to full dose was given to 22 (88%) patients for six weeks or longer, and analgesics in low or moderate doses were given to twelve (48%) patients at discharge. The major amputation rate at 1 year was 8% among conservatively treated patients, and four patients with foot embolization had not undergone amputation at 1 year. CONCLUSION: Patients selected for initial conservative therapy of ALI with anticoagulation alone may have a good outcome, even when admitted with Rutherford class IIb ischemia. A low C-reactive protein level at admission seems to be a favorable marker when choosing conservative therapy. A prospective, preferably multicenter, study with a predefined protocol in these conservatively treated patients is warranted to better define the dose and length of anticoagulation therapy.

[Vascular occlusion following profile harmonization of the chin with hyaluronic acid fillers]. / Vasculaire occlusie na profielharmonisatie van de kin met hyaluronzuur fillers.

The use of dermal fillers for cosmetic procedures has increased rapidly both worldwide and in the Netherlands in recent years, which has led to an absolute increase in reported side effects and complications. Although most of these complications are mild, serious complications such as vascular occlusion can also occur. In this article, we describe a case of a 35-year-old woman who showed signs of reduced tissue perfusion and the early stage of skin necrosis following injection of hyaluronic acid fillers in the chin. This complication was successfully treated by ultrasound-guided injection of hyaluronidase, resulting in a full recovery without residual symptoms. To minimize the risk of serious complications treatment with hyaluronic acid fillers should be carried out by an experienced practitioner.

Part II: Cutaneous manifestations of peripheral vascular disease.

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent globally, it is essential for dermatologists to become competent at accurately recognizing and diagnosing cutaneous manifestations and directing individuals to receive appropriate care and treatment.

Complications following surgical treatment of posterior malleolar fractures: an analysis of 300 cases.

AIMS: The treatment of ankle fractures and fracture-dislocations involving the posterior malleolus (PM) has undergone considerable changes over the past decade. The aim of our study was to identify risk factors related to the occurrence of complications in surgically treated ankle fractures with PM involvement. PATIENTS AND METHODS: We retrospectively analyzed 300 patients at a mean age of 57 years with 300 ankle fractures involving the PM treated surgically at our institution over a 12-year period. The following relevant comorbidities were noted: arterial hypertension (43.7%; n = 131), diabetes mellitus (DM) (14.0%; n = 42), thereof insulin-dependent (3.7%; n = 11), peripheral vascular disease (0.7%; n = 2), osteoporosis (12.0%; n = 36), dementia (1.0%; n = 3), and rheumatoid arthritis (2.0%; n = 6). Furthermore, nicotine consumption was recorded in 7.3% (n = 22) and alcohol abuse in 4.0% (n = 12). RESULTS: Complications occurred in 41 patients (13.7%). A total of 20 (6.7%) revision surgeries had to be performed. Patients with DM (p < 0.001), peripheral vascular disease (p = 0.003) and arterial hypertension (p = 0.001) had a significantly increased risk of delayed wound healing. Alcohol abuse was associated with a significantly higher overall complication rate (OR 3.40; 95% CI 0.97-11.83; p = 0.043), increased rates of wound healing problems (OR 11.32; 95% CI 1.94-65.60; p = 0.001) and malalignment requiring revision (p = 0.033). The presence of an open fracture was associated with an increased rate of infection and wound necrosis requiring revision (OR 14.25; 95% CI 2.39-84.84; p < 0.001). Multivariate analysis identified BMI (p = 0.028), insulin-dependent DM (p = 0.003), and staged fixation (p = 0.043) as independent risk factors for delayed wound healing. Compared to the traditional lateral approach, using the posterolateral approach for fibular fixation did not lead to increased complication rates. CONCLUSIONS: Significant risk factors for the occurrence of complications following PM fracture treatment were identified. An individually tailored treatment regimen that incorporates all risk factors is important for a good outcome.

Impact factors of POCUS-guided cannulation for peripheral venoarterial extracorporeal membrane oxygenation: One single-center retrospective clinical analysis.

We aimed to evaluate associated factors for point-of-care ultrasound (POCUS)-guided percutaneous catheterization for venoarterial extracorporeal membrane oxygenation (VA-ECMO). VA-ECMO cases from March 2018 to October 2020 in Department of Intensive Care Unit, Binhaiwan Central Hospital of Dongguan, were enrolled. Clinical data, outcomes, and complications were recorded and summarized. Fifty-nine cases were enrolled, among which 88.1% succeeded in POCUS-guided catheterization via Seldinger technique, whereas 59.3% succeeded at the first puncture. Results showed that artery diameter and times of arterial punctures were independent associated factors for Seldinger puncture (P = .018, odds ratio [OR] = 23.374, 95% confidence interval [CI] = 1.706-320.270; P = .031, OR = 145.098, 95% CI = 1.592-13220.980), and artery diameter and cardiac ejection fraction value (≥30%/<30%) were independent associated factors for first puncture (P = .044, OR = 1.622, 95% CI = 1.014-2.596; P = .013, OR = 5.565, 95% CI = 1.441-21.488). For extracorporeal cardiopulmonary resuscitation patients, artery diameter was independent associated factor for Seldinger puncture (P = .022, OR = 2.070, 95% CI = 1.110-3.858), and cardiac ejection fraction value (≥30%/<30%) was independent associated factor for first puncture (P = .007, OR = 9.533, 95% CI = 1.847-49.204). Thirteen patients (22.0%) had local hemorrhage post puncture, 8 patients (13.6%) presented distal limb arterial ischemia, and 8 patients (13.6%) suffered puncture-related thrombosis. Vasoactive Inotropic Score was found to be independent associated factor for local hemorrhage (P = .039, OR = 0.994, 95% CI = 0.988-1.000), and the Acute Physiology and Chronic Health Evaluation II score was independent associated factor for thrombosis (P = .025, OR = 0.935, 95% CI = 0.882-0.992). Diabetes and cardiopulmonary resuscitation time before catheterization were independent factors for distal limb ischemia (P = .026, OR = 220.774, 95% CI = 1.905-25591.327; P = .017, OR = 1.054, 95% CI = 1.009-1.101). POCUS-guided percutaneous catheterization via Seldinger technique can be the first choice for VA-ECMO cannulation, especially for a team without angiotomy qualifications. Before cannulation, evaluating the target artery and heart function by ultrasound can help predict outcome of catheterization. Assessing risk factors (diabetes, cardiopulmonary resuscitation time before catheterization, Vasoactive Inotropic Score, the Acute Physiology and Chronic Health Evaluation II score) is helpful for prevention and treatment of complications.

COVID19 vaccination in adults with sickle cell disease is not associated with increases in rates of pain crisis.

ABSTRACTPeople with sickle cell disease (SCD) are more vulnerable to hospitalization, pneumonia, and pain following COVID-19 infection. However, given the association between the inflammatory response and vaso-occlusive crises in SCD and a case report of vaso-occlusive crises following administration of the ChAdOx1 nCov-195-7/AstraZeneca vaccine, there is concern that the administration of COVID-19 vaccines in people with SCD might provoke a vaso-occlusive crisis. To address this critical gap in knowledge, we sought to examine acute care usage for vaso-occlusive crisis and frequency and severity of side effects following COVID-19 vaccination among patients at the Montefiore Sickle Cell Center for Adults. As part of regular care, patients were asked if they had received COVID-19 vaccination and any side effects were noted. Electronic medical records were reviewed for the type of vaccine, dates received, episodes of vaso-occlusive crises within seven days of a dose, and side effects noted. The risk of average hospital utilization per week in 2019 was calculated as a baseline. We found that fewer than 1 in 10 patients presented to the hospital within seven days of vaccination and that the risk of hospital utilization was similar to the average risk in a week in 2019. Of patients who reported side effects, one reported a possible case of sensorineural hearing loss otherwise no other rare side effects, including thrombosis or death, were reported.

Trans tibial amputation with or without a tourniquet in patients with diabetic foot infection and peripheral vascular disease: Comparison of postoperative outcomes.

Background: Transtibial amputation (TTA) due to complications of diabetic foot infection (DFI) or peripheral vascular disease (PVD) is a high-risk procedure in fragile patients. The risks of reoperation, blood loss requiring blood transfusion, and mortality are high. The use of a tourniquet in this procedure is controversial and scarcely reported. Objective: this study aimed to compare the outcomes of TTAs with or without a tourniquet in a single tertiary medical center. Methods: We retrospectively identified all patients who had undergone TTA in our institution (1/2019-1/2020) and included only those who underwent the procedure due to complications of DFI or PVD (n = 69). The retrieved data included demographics, comorbidities, ASA score, the use of a tourniquet, operation duration, pre- and postoperative hemoglobin levels, administration of blood transfusions, hospitalization length, surgical site infection and 60-days reoperation and mortality rates. Results: TTA with a tourniquet was superior to TTA without a tourniquet in reducing the average operation length by 11 min (p = 0.05), the median postoperative hospitalization by 6 days (p = 0.04), and the use of blood transfusions (odds ratio [OR] = 0.176, 95% confidence interval [CI]: 0.031-0.996). Conclusions: Our findings demonstrated advantages in operative time, hospitalization length, and blood transfusion requirement for TTA with a tourniquet compared to TTA without a tourniquet.

Estimating risk factor progression equations for the UKPDS Outcomes Model 2 (UKPDS 90).

OBJECTIVES: To estimate 13 equations that predict clinically plausible risk factor time paths to inform the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model version 2 (UKPDS-OM2). METHODS: Data from 5102 UKPDS participants from the 20-year trial, and the 4031 survivors with 10 years further post-trial follow-up, were used to derive equations for the time paths of 13 clinical risk factors: HbA1c , systolic blood pressure, LDL-cholesterol, HDL-cholesterol, BMI, micro- or macro-albuminuria, creatinine, heart rate, white blood cell count, haemoglobin, estimated glomerular filter rate, atrial fibrillation and peripheral vascular disease (PVD). The incidence of events and death predicted by the UKPDS-OM2 when informed by the new risk factor equations was compared with the observed cumulative rates up to 25 years. RESULTS: The new equations were based on 24 years of follow-up and up to 65,252 person-years of data. Women were associated with higher values of all continuous risk factors except for haemoglobin. Older age and higher BMI at diagnosis were associated with higher rates of PVD (HR 1.06 and 1.02), atrial fibrillation (HR 1.10 and 1.08) and micro- or macro-albuminuria (HR 1.01 and 1.18). Smoking was associated with higher rates of developing PVD (HR 2.38) and micro- and macro-albuminuria (HR 1.39). The UKPDS-OM2, informed by the new risk factor equations, predicted event rates for complications and death consistent with those observed. CONCLUSIONS: The new equations allow risk factor time paths beyond observed data, which should improve modelling of long-term health outcomes for people with type 2 diabetes when using the UKPDS-OM2 or other models.

Long-term incidence of upper extremity venous obstruction in implantable cardioverter defibrillator patients.

BACKGROUND: Very little is known about the long-term prevalence of severe venous obstruction and occlusion in patients with transvenous implantable cardioverter-defibrillator leads. The objective of the current investigation was to elucidate the incidence and prevalence and to identify predisposing conditions in an ICD cohort over a long follow-up period. METHODS: Based on a prospective database, we analyzed consecutive patients who received an ICD implantation in our hospital between 06/1988 and 2009 as well as all corresponding follow-up data until 02/2018. Cavographies were used for analysis, and all patients with at least one device replacement and one follow-up cavography were included. RESULTS: Over a mean follow-up period of 94 ± 50 months, severe venous obstruction was found in 147 (33%) of 448 patients. Kaplan-Meier analysis shows a severe obstruction or occlusion in 50% of patients after a period of 14.3 years. The total number of leads (p < .001, HR 2.01, CI 2.000-2.022), an advanced age (p = .004, HR 1.023 per year, CI 1.022-1.024) and the presence of dilated cardiomyopathy (p = .035, HR 1.49, CI 1.47-1.51) were predictive of venous obstruction whereas the presence of anticoagulation was not. CONCLUSION: Severe obstruction of the access veins after ICD implantation occurs frequently and its prevalence shows a nearly linear increase over long-time follow-up. Multiple leads, an advanced age and DCM as underlying disease are associated with an increased risk of venous obstruction while the role of anticoagulation to prevent venous obstruction in ICD patients is unclear.

Norepinephrine-Induced Peripheral Ischemia Leading to Gangrene: A Case Series.

ABSTRACT: Norepinephrine is used in the acute care setting to establish and maintain hemodynamic stability in patients with hypotension. Although it is often a lifesaving medication, norepinephrine may lead to profound vascular insufficiency in the extremities, resulting in dry gangrene and skin necrosis. The purpose of this article is to present a case series of skin complications related to treatment with norepinephrine and review the pathophysiology behind these complications. The authors also explore risk stratification as it relates to history and clinical presentation with subsequent focus on contingencies to mitigate the adverse effects of vasoconstriction on peripheral tissues.

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects.

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G-Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.

Repercusiones directas e indirectas de la COVID-19 en los portadores de enfermedades vasculares periféricas / Direct and Indirect Repercussions of COVID-19 in Patients with Peripheral Vascular Diseases

Si bien el virus SARS-CoV-2, causante de la enfermedad COVID-19, afecta con preferencia el sistema respiratorio, son muchos los informes sobre los efectos sistémicos que puede provocar, donde el sistema vascular no está exento. No obstante, también la aparición de este Coronavirus ha reformulado en el mundo el funcionamiento de los sistemas de salud a todos los niveles, lo que ha afectado de manera indirecta a aquellos que portan alguna enfermedad vascular periférica(AU)

Peripheral vascular complications following totally endoscopic cardiac surgery.

BACKGROUND: Clinical application of minimally invasive cardiac surgery has increased annually. Cardiopulmonary bypass is established by peripheral cannulation during minimally invasive cardiac surgery. The methodology of peripheral cannulation has unique characteristics, which have associated risks and complications. Few studies have been conducted on this topic. In this study, we focused on complications of peripheral cannulation in totally endoscopic cardiac surgery. METHODS: Patients who underwent totally endoscopic cardiac surgery with cardiopulmonary bypass established by peripheral cannulation at our institution between January 2019 and June 2020 were reviewed. Specific cannulation strategies and related cannulation complications were noted. RESULTS: One hundred forty-eight patients underwent totally endoscopic cardiac surgery. One hundred forty-eight cannulations were performed in the femoral artery and vein, and eleven were performed in the internal jugular vein (combined with the femoral vein). The median size of the femoral artery cannula was 22Fr, and that of the venous canula was 24Fr. One patient died of retroperitoneal haematoma due to femoral artery injury. Three patients had postoperative lower limb oedema. One patient had a postoperative diagnosis of femoral vein thrombosis. CONCLUSIONS: Different from cannulation in patients with aortic dissection and aneurysms, femoral artery cannulation is safe in totally endoscopic cardiac surgery. Venous cannulation is characterized by a large-bore venous cannula and a short period of use. There are few reports about complications of venous cannulation. The main complication in this study was mechanical injury, and the key to preventing this injury is meticulous manipulation during surgery.

Dermatopatología de la oclusión intraluminal vascular: parteII (coagulopatías, émbolos y miscelánea) / Clinical and Histopathologic Characteristics of the Main Causes of Vascular Occusion - Part II: Coagulation Disorders, Emboli, and Other

La patología vascular oclusiva es causante de diversas y variadas manifestaciones clínicas, algunas de ellas con catastróficas consecuencias para el paciente. Dado que las causas de tal oclusión son muy variadas, hemos abordado en un artículo previo reciente en esta misma revista las causas trombóticas. En el presente artículo recopilamos diversas causas adicionales de oclusión intravascular

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in part I of this review. In this second part, we look at additional causes of vascular occlusion

Long-term incidence and outcomes of obesity-related peripheral vascular disease after bariatric surgery.

BACKGROUND AND AIMS: Patients with obesity are at high risk of suffering from arterial and venous peripheral vascular disease (PVD). Bariatric surgery is an effective strategy to achieve weight reduction for patients with obesity. The long-term impact of bariatric surgery on obesity-related morbidity is subject to increasing research interest. This study aimed to ascertain the impact of bariatric surgery on the long-term occurrence of PVD in patients with obesity. METHODS: The study population was extracted from the Clinical Practice Research Datalink, a nation-wide database containing primary and secondary care records of consenting patients. The intervention cohort was 2959 patients who had undergone bariatric surgery during follow-up; their controls were 2959 propensity-score-matched counterparts. The primary endpoint was development of any PVD: arterial or venous. Secondary endpoints were incident peripheral arterial disease alone, incident peripheral venous disease alone. RESULTS: Three hundred forty-six patients suffered a primary endpoint during follow-up. Bariatric surgery did not improve peripheral vascular disease rates as a whole, but it was associated with significantly lower event rates of arterial disease (HR = 0.560, 95%CI 0.327-0.959, p = 0.035) but higher event rates of venous disease (HR = 1.685, 95%CI 1.256-2.262, p < 0.001). CONCLUSIONS: Bariatric surgery was associated with significantly reduced long-term occurrence of arterial disease but increased occurrence of venous disease in patients with obesity.

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

AIMS/HYPOTHESIS: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes. METHODS: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593). RESULTS: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001). CONCLUSIONS/INTERPRETATION: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.

Metabolic syndrome in type 1 diabetes and its association with diabetes complications.

AIM: To assess the prevalence of metabolic syndrome in type 1 diabetes, and its age-related association with diabetes complications. METHODS: Australian National Diabetes Information Audit and Benchmarking (ANDIAB) was a well-established quality audit programme. It provided cross-sectional data on people attending specialist diabetes services across Australia. We determined the prevalence of metabolic syndrome (WHO criteria) in adults with type 1 diabetes and its associations with diabetes complications across age groups. RESULTS: Metabolic syndrome prevalence was 30% in 2120 adults with type 1 diabetes. Prevalence increased with age: 21% in those aged <40 years, 35% in those aged 40-60 years, and 44% in those aged >60 years (P<0.001), which was driven by an increase in hypertension rate. Metabolic syndrome was associated with a higher prevalence of microvascular, macrovascular and foot complications, with the greatest impact at a younger age. The odds ratio for macrovascular complications with metabolic syndrome, compared with without, was 5.9 (95% CI 2.1-16.4) in people aged <40 years, 2.7 (95% CI 1.7-4.2) in those aged 40-60 years, and 1.7 (95% CI 1.1-2.7) in those aged >60 years (all P < 0.05). Metformin use was higher in those with metabolic syndrome (16% vs 4%; P<0.001). CONCLUSIONS: In this large Australian cohort, metabolic syndrome was common in type 1 diabetes and identified people at increased risk of the spectrum of diabetes complications, particularly in young to middle-aged adults. Potential clinical implications are that therapies targeting insulin resistance in this high-risk group may reduce diabetes complications and should be explored.