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1.
J Vasc Surg ; 79(6): 1457-1465, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38286153

ABSTRACT

OBJECTIVE: Cryopreserved (CP) products are utilized during challenging cases when autogenous or prosthetic conduit use is not feasible. Despite decades of experience with cadaveric greater saphenous vein (GSV), there is limited available data regarding the outcomes and patency of other CP products, specifically arterial and deep venous grafts. This study was designed to evaluate outcomes of non-GSV CP conduits in patients undergoing urgent, emergent, and elective arterial reconstruction at our institution. We hypothesized that non-GSV CP allografts have adequate patency and outcomes and are therefore a feasible alternative to GSV in settings where autologous graft is unavailable or prosthetic grafts are contraindicated. METHODS: This study was approved by the Institutional Review Board at our institution. We retrospectively reviewed charts of patients undergoing arterial reconstructions using CP conduits from 2010 to 2022. Data collected included demographics, comorbidities, smoking status, indications for surgery, indication for CP conduit use, anatomic reconstruction, urgency of procedure, and blood loss. Time-to-event outcomes included primary and secondary graft patency rates, follow-up amputations, and mortality; other complications included follow-up infection/reinfection and 30-day complications, including return to the operating room and perioperative mortality. Time-to-event analyses were evaluated using product-limit survival estimates. RESULTS: Of 96 identified patients receiving CP conduits, 56 patients received non-GSV conduits for 66 arterial reconstructions. The most common type of non-GSV CP product used was femoral artery (31 patients), followed by aorto-iliac artery (22 patients), and femoral vein (19 patients), with some patients receiving more than one reconstruction or CP product. Patients were mostly male (75%), with a mean age of 63.1 years and a mean body mass index of 26.7 kg/m2. Indications for CP conduit use included infection in 53 patients, hostile environment in 36 patients, contaminated field in 30 patients, tissue coverage concerns in 30 patients, inadequate conduit in nine patients, and patient preference in one patient. Notably, multiple patients had more than one indication. Most surgeries (95%) were performed in urgent or emergent settings. Supra-inguinal reconstructions were most common (53%), followed by extra-anatomic bypasses (47%). Thirty-day mortality occurred in 10 patients (19%). Fifteen patients (27%) required return to the operating room for indications related to the vascular reconstructions, with 10 (18%) cases being unplanned and five (9%) cases planned/staged. Overall survival at 6, 12, and 24 months was 80%, 68%, and 59%, respectively. Primary patency at 6, 12, and 24 months was 86%, 70%, and 62%, respectively. Amputation freedom at 6 months, 12 months, and 24 months was 98%, 95%, and 86%, respectively for non-traumatic indications. CONCLUSIONS: Non-GSV CP products may be used in complex arterial reconstructions when autogenous or prosthetic options are not feasible or available.


Subject(s)
Cryopreservation , Vascular Patency , Humans , Retrospective Studies , Male , Female , Aged , Middle Aged , Time Factors , Treatment Outcome , Risk Factors , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Arteries/surgery , Arteries/transplantation , Amputation, Surgical , Peripheral Arterial Disease/surgery , Peripheral Arterial Disease/physiopathology , Peripheral Arterial Disease/diagnostic imaging , Limb Salvage , Plastic Surgery Procedures/adverse effects , Plastic Surgery Procedures/methods , Aged, 80 and over , Blood Vessel Prosthesis , Postoperative Complications/etiology
2.
J Clin Endocrinol Metab ; 109(2): e726-e734, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-37690117

ABSTRACT

CONTEXT: Uric acid's role in cardiovascular health in youth with type 1 diabetes is unknown. OBJECTIVE: Investigate whether higher uric acid is associated with increased blood pressure (BP) and arterial stiffness over time in adolescents and young adults with type 1 diabetes and if overweight/obesity modifies this relationship. METHODS: Longitudinal analysis of data from adolescents and young adults with type 1 diabetes from 2 visits (mean follow up 4.6 years) in the SEARCH for Diabetes in Youth multicenter prospective cohort study from 2007 to 2018. Our exposure was uric acid at the first visit and our outcome measures were the change in BP, pulse wave velocity (PWV), and augmentation index between visits. We used multivariable linear mixed-effects models and assessed for effect modification by overweight/obesity. RESULTS: Of 1744 participants, mean age was 17.6 years, 49.4% were female, 75.9% non-Hispanic White, and 45.4% had a follow-up visit. Mean uric acid was 3.7 mg/dL (SD 1.0). Uric acid was not associated with increased BP, PWV-trunk, or augmentation index over time. Uric acid was marginally associated with PWV-upper extremity (ß = .02 m/s/year, 95% CI 0.002 to 0.04). The magnitude of this association did not differ by overweight/obesity status. CONCLUSION: Among adolescents and young adults with type 1 diabetes, uric acid was not consistently associated with increased BP or arterial stiffness over time. These results support findings from clinical trials in older adults with diabetes showing that lowering uric acid levels does not improve cardiovascular outcomes.


Subject(s)
Diabetes Mellitus, Type 1 , Vascular Stiffness , Young Adult , Humans , Female , Adolescent , Aged , Male , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Uric Acid , Risk Factors , Overweight/complications , Pulse Wave Analysis , Prospective Studies , Obesity/complications , Vascular Stiffness/physiology , Blood Pressure
3.
Clin Diabetes ; 41(2): 177-184, 2023.
Article in English | MEDLINE | ID: mdl-37092149

ABSTRACT

Preconception counseling is recommended for all women with diabetes starting at puberty to convey the importance of optimal diabetes management for maternal and fetal outcomes. This study included 622 female participants from the SEARCH for Diabetes in Youth study with a mean age of 22.2 years (range 14-35 years). Only 53.7% reported ever receiving preconception counseling, which was significantly lower among women seeing pediatric providers than those seeing adult or all-age providers. Older age and history of prior pregnancy were associated with increased odds of reporting having received preconception counseling. Identification of barriers to delivering preconception counseling to young females with diabetes and strategies to overcome them are needed to reduce the risk for pregnancy complications and adverse offspring health outcomes.

4.
Pediatr Diabetes ; 20232023.
Article in English | MEDLINE | ID: mdl-38706530

ABSTRACT

Aims/hypotheses: People with type 1 (T1D) or type 2 diabetes (T2D) who also have diabetes complications can have pronounced cognitive deficits. It remains unknown, however, whether and how multiple diabetes complications co-occur with cognitive dysfunction, particularly in youth-onset diabetes. Methods: Using data from the SEARCH for Diabetes in Youth study cohort, a prospective longitudinal cohort, we examined clustering of complications and their underlying clinical factors with performance on cognitive tests in young adults with youth-onset T1D or T2D. Cognition was assessed via the NIH Toolbox Cognition Battery. The main cognitive variables were age-corrected scores for composite fluid cognition and associated cognitive subdomains. Diabetes complications included retinopathy, microalbuminuria, and peripheral neuropathy (PN). Lipids, systolic blood pressure (SBP), hemoglobin A1c, and other clinical factors were included in the analyses. Clustering was applied separately to each group (T1D=646; T2D=165). A three-cluster(C) solution was identified for each diabetes type. Mean values and frequencies of all factors were compared between resulting clusters. Results: The average age-corrected score for composite fluid cognition differed significantly across clusters for each group (p<0.001). People with T1D and the lowest average fluid cognition scores had the highest frequency of self-reporting at least one episode of hypoglycemia in the year preceding cognitive testing and the highest prevalence of PN. Persons with T2D and the lowest average fluid cognition scores had the highest SBP, the highest central systolic and diastolic blood pressures, and highest prevalence of PN. Conclusions/interpretations: These findings highlight shared (PN) and unique factors (hypoglycemia in T1D; SBP in T2D) that could be targeted to potentially mitigate cognitive issues in young people with youth-onset diabetes.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/psychology , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/psychology , Male , Female , Young Adult , Adolescent , Longitudinal Studies , Adult , Prospective Studies , Cognition/physiology , Diabetes Complications/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/etiology
5.
Ann Vasc Surg ; 87: 286-294, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35817384

ABSTRACT

BACKGROUND: Autogenous arteriovenous fistula (AVF) remains the standard of hemodialysis (HD) access; however, it cannot be reasonably obtained in all patients. For patients with contraindications to AVFs, prosthetic arteriovenous graft (AVG) remains an alternative. AVGs are plagued by high failure rates; however, there is a paucity of literature examining this. This study aims to examine a single-center review of outcomes of forearm loop AVGs in patients requiring HD access. METHODS: A single institution, retrospective chart review was completed from 2012 to 2019, including demographics, end-stage renal disease etiology, brachial vessel diameters, and comorbidities. Logistic regression and Cox proportional hazard models were evaluated. Outcomes were defined as primary patency (time elapsed from graft creation until it was utilized as the patient's primary access), primary-assisted patency (time from primary access to intervention to maintain patency), and functional patency (time from graft placement until graft failure). Additionally, multinomial regression models were used to evaluate associations with categorical number of required interventions. RESULTS: Ninety-eight patients [mean age 61.8 (13.9) years, 42.9% female] were identified as having brachial artery to brachial vein AVG creation during the study period, of which 75% achieved primary patency. Primary-assisted patency was 0.36 [standard error (SE) 0.07] at 6 months and 0.12 (SE 0.05) at 1 year. Functional patency was 0.75 (SE 0.07) at 6 months and 0.43 (SE 0.09) at 1 year. No association between preoperative vessel diameters and primary-assisted or functional patency was observed. Interestingly, there was a significant negative association between previous ipsilateral access and achievement of primary patency with a 60% decrease in odds of achieving primary patency in patients with previous ipsilateral access [odds ratio 0.4, 95% confidence interval (CI) 0.1-0.9, P = 0.03]. There was also noted to be a significant association between the presence of an ipsilateral catheter and increased risk of subsequent abandonment of the AVG (hazard ratio 2.6, 95% CI 1.1-5.8, P = 0.02). CONCLUSIONS: Prosthetic forearm loop AVGs remain hindered in their utility as they show high rates of graft failure within a year of creation. A significant patient-specific factor leading to this was not clearly demonstrated. As guidelines change regarding the nature of dialysis access for patients on HD, these results draw into question the utility of prosthetic forearm loop grafts in patients requiring long-term HD access.


Subject(s)
Arteriovenous Shunt, Surgical , Blood Vessel Prosthesis Implantation , Humans , Female , Middle Aged , Male , Arteriovenous Shunt, Surgical/adverse effects , Arteriovenous Shunt, Surgical/methods , Forearm/blood supply , Vascular Patency , Graft Occlusion, Vascular/diagnostic imaging , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/therapy , Retrospective Studies , Blood Vessel Prosthesis Implantation/adverse effects , Risk Factors , Treatment Outcome , Time Factors , Renal Dialysis/adverse effects
6.
J Vasc Surg ; 75(1): 186-194, 2022 01.
Article in English | MEDLINE | ID: mdl-34478808

ABSTRACT

OBJECTIVE: Opiate use, dependence, and the associated morbidity and mortality are major current public health problems in the United States. Little is known about patterns of opioid use in patients with peripheral arterial disease (PAD). The purpose of this study was to identify the prevalence of chronic preoperative and postoperative prescription opioid use in patients with PAD. A secondary aim was to determine the demographic, comorbid conditions, and operative characteristics associated with chronic opioid use. METHODS: Using a single-institution database of patients with PAD undergoing open or endovascular lower extremity intervention from 2013 to 2014, data regarding opiate use and associated conditions were abstracted for analysis. Patients were excluded if they did not live in North Carolina or surgery was not for PAD. Preoperative (PreCOU) and postoperative chronic opioid use (PostCOU) were defined as consistent opioid prescription filling in the 3 months before and after the index procedure, respectively. Opioid prescription filling was assessed using the North Carolina Controlled Substance Reporting System. Demographics, comorbid conditions, other adjunct pain medication data, and operative characteristics were abstracted from our institutional electronic medical record. Associations with PreCOU were evaluated using the t test, Wilcoxon test, or two-sample median test (continuous), or the χ2 or Fisher exact tests (categorical). RESULTS: A total of 202 patients undergoing open (108; 53.5%) or endovascular (94; 46.5%) revascularization for claudication or critical limb ischemia were identified for analysis. The mean age was 64.6 years, and 36% were female. Claudication was the indication for revascularization in 26.7% of patients, and critical limb ischemia was the indication in 73.3% of patients. The median preoperative ankle-brachial index (ABI) was 0.50. Sixty-eight patients (34%) met the definition for PreCOU. PreCOU was associated with female gender, history of chronic musculoskeletal pain, benzodiazepine use, and self-reported illicit drug use. Less than 50% of patients reported use of non-opiate adjunct pain medications. No association was observed between PreCOU and pre- or postoperative ABI, or number of prior lower extremity interventions. Following revascularization, the median ABI was 0.88. PreCOU was not associated with significant differences in postoperative complications, length of stay, or mortality. Overall, 71 patients (35%) met the definition for PostCOU, 14 of whom had no history of preoperative chronic opiate use. Ten patients with PreCOU did not demonstrate PostCOU. CONCLUSIONS: Chronic opiate use was common in patients with PAD with a prevalence of approximately 35%, both prior to and following revascularization. Revascularization was associated with a termination of chronic opiate use in less than 15% of patients with PreCOU. Additionally, 10% of patients who did not use opiates chronically before their revascularization did so afterwards. Patients with PAD requiring intervention represent a high-risk group with regards to chronic opiate use. Increased diligence in identifying opioid use among patients with PAD and optimizing the use of non-narcotic adjunct pain medications may result in a lower prevalence of chronic opiate use and its attendant adverse effects.


Subject(s)
Analgesics, Opioid/therapeutic use , Angioplasty/adverse effects , Chronic Limb-Threatening Ischemia/surgery , Intermittent Claudication/surgery , Pain, Postoperative/drug therapy , Aged , Angioplasty/statistics & numerical data , Chronic Limb-Threatening Ischemia/complications , Drug Prescriptions/statistics & numerical data , Female , Humans , Intermittent Claudication/complications , Lower Extremity/blood supply , Lower Extremity/surgery , Male , Middle Aged , North Carolina/epidemiology , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Postoperative Period , Preoperative Period , Prevalence , Retrospective Studies , Risk Factors , Treatment Outcome
7.
Diabetes Care ; 2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34376501

ABSTRACT

OBJECTIVE: To identify correlates of hemoglobin A1c (HbA1c) testing frequency and associations with HbA1c levels and microvascular complications in youth-onset diabetes. RESEARCH DESIGN AND METHODS: The SEARCH for Diabetes in Youth study collected data from individuals diagnosed with diabetes before age 20 at 8 years (n=1,885 type 1, n=230 type 2) and 13 years (n=649 type 1, n = 84 type 2) diabetes duration. We identified correlates of reporting ≥3 HbA1c tests/year using logistic regression. We examined associations of HbA1c testing with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) using sequentially adjusted linear and logistic regression. RESULTS: For type 1 diabetes, odds of reporting ≥3 HbA1c tests/year at 8 and 13 years diabetes duration decreased with older age at diagnosis (odds ratio [OR] 0.91 [95% CI 0.88-0.95]), longer duration of diabetes (OR 0.90 [0.82-0.99]), not having a personal doctor (OR 0.44 [0.30-0.65]), and lapses in health insurance (OR 0.51 [0.27-0.96]). HbA1c testing ≥3 times/year over time was associated with lower HbA1c levels (OR -0.36% [-0.65 to -0.06]) and lower odds of microvascular complications (OR 0.64 [0.43-0.97]) at 13 years duration, but associations were attenuated after adjustment for HbA1c testing correlates (OR -0.17 [-0.46 to 0.13] and 0.70 [0.46-1.07], respectively). For type 2 diabetes, not seeing an endocrinologist decreased the odds of reporting ≥3 HbA1c tests/year over time (OR 0.19 [0.06-0.63]), but HbA1c testing frequency was not associated with HbA1c levels or microvascular complications. CONCLUSIONS: We observed disparities in HbA1c testing frequency predominately by health care-related factors, which were associated with diabetes outcomes in type 1 diabetes.

8.
Pediatr Diabetes ; 22(7): 951-959, 2021 11.
Article in English | MEDLINE | ID: mdl-34363298

ABSTRACT

BACKGROUND: Dyslipidemia has been documented in youth with type 2 diabetes. There is a paucity of studies examining dyslipidemia over time in youth with type 2 diabetes and associated risk factors. OBJECTIVE: To evaluate lipids at baseline and follow-up and associated risk factors in youth with type 2 diabetes. METHODS: We studied 212 youth with type 2 diabetes at baseline and after an average of 7 years of follow-up in the SEARCH for Diabetes in Youth Study. Abnormal lipids were defined as high-density lipoprotein cholesterol (HDL-C) < 35, low-density lipoprotein cholesterol (LDL-C) > 100, or triglycerides >150 (all mg/dl). We evaluated participants for progression to abnormal lipids (normal lipids at baseline and abnormal at follow-up), regression (abnormal lipids at baseline and normal at follow-up), stable normal, and stable abnormal lipids over time for HDL-C, LDL-C, and triglycerides. Associations between hemoglobin A1c (HbA1c) and adiposity over time (area under the curve [AUC]) with progression and stable abnormal lipids were evaluated. RESULTS: HDL-C progressed, regressed, was stable normal, and stable abnormal in 12.3%, 11.3%, 62.3%, and 14.2% of participants, respectively. Corresponding LDL-C percentages were 15.6%, 12.7%, 42.9%, and 28.8% and triglycerides were 17.5%, 10.8%, 55.7%, and 16.0%. Each 1% increase in HbA1c AUC was associated with a 13% higher risk of progression and stable abnormal triglycerides and a 20% higher risk of progression and stable abnormal LDL-C. Higher adiposity AUC was marginally (p = 0.049) associated with abnormal HDL-C. CONCLUSIONS: Progression and stable abnormal LDL-C and triglycerides occur in youth with type 2 diabetes and are associated with higher HbA1c.


Subject(s)
Diabetes Mellitus, Type 2/blood , Dyslipidemias/epidemiology , Glycemic Control/statistics & numerical data , Adolescent , Adult , Child , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Dyslipidemias/complications , Female , Glycated Hemoglobin/analysis , Humans , Male , Risk Factors , Triglycerides/blood , Young Adult
9.
Diabetes Care ; 44(7): 1573-1578, 2021 07.
Article in English | MEDLINE | ID: mdl-34099516

ABSTRACT

OBJECTIVE: We previously reported a high (˜30%) but stable prevalence of diabetic ketoacidosis (DKA) at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed. RESEARCH DESIGN AND METHODS: We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010-2016) (n = 7,612 incident diabetes cases; mean [SD] age 10.1 [4.5] at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (RR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH for Diabetes in Youth Study site. RESULTS: DKA prevalence increased from 35.3% (95% CI 32.2, 38.4) in 2010 to 40.6% (95% CI 37.8, 43.4) in 2016 (P trend = 0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR 1.02 [95% CI 1.01, 1.04] and adjusted RR 1.02 [95% CI 1.01, 1.04]; P = 0.01 for both). CONCLUSIONS: Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002 to 2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Adolescent , Child , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diabetic Ketoacidosis/diagnosis , Diabetic Ketoacidosis/epidemiology , Diabetic Ketoacidosis/etiology , Ethnicity , Humans , Prevalence
10.
Diabetes Care ; 44(6): 1273-1280, 2021 06.
Article in English | MEDLINE | ID: mdl-33905344

ABSTRACT

OBJECTIVE: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285). RESEARCH DESIGN AND METHODS: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition. RESULTS: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively). CONCLUSIONS: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.


Subject(s)
Diabetes Mellitus, Type 2 , Adolescent , Child , Cognition , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Humans , Obesity , Parents , Young Adult
12.
Nat Commun ; 12(1): 24, 2021 01 05.
Article in English | MEDLINE | ID: mdl-33402679

ABSTRACT

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.


Subject(s)
Anorexia Nervosa/genetics , Blood Glucose/metabolism , Glucose Intolerance/genetics , Insulin Receptor Substrate Proteins/genetics , Insulin Resistance/genetics , Insulin/blood , Kruppel-Like Transcription Factors/genetics , Adult , Anorexia Nervosa/blood , Anorexia Nervosa/ethnology , Anorexia Nervosa/physiopathology , Fasting/blood , Female , Gene Expression , Genetic Loci , Genome-Wide Association Study , Glucose Intolerance/blood , Glucose Intolerance/ethnology , Glucose Intolerance/physiopathology , Humans , Insulin Receptor Substrate Proteins/blood , Kruppel-Like Transcription Factors/blood , Male , Middle Aged , Phenotype , Sex Characteristics , Sex Factors , Waist-Hip Ratio , White People
13.
Pediatr Diabetes ; 21(7): 1093-1101, 2020 11.
Article in English | MEDLINE | ID: mdl-32737919

ABSTRACT

AIMS: Examine associations of dietary strategies used to manage diabetes over time with hemoglobin A1c in youth-onset type 1 or type 2 diabetes. METHODS: The SEARCH for Diabetes in Youth observational study assessed dietary strategies used by 1814 participants with diabetes (n = 1558 type 1, n = 256 type 2) at two to three research visits over 5.5 years (range 1.7-12.2). Participants reported often, sometimes, or never using 10 different dietary strategies, and use over time was categorized into five mutually exclusive groups: often using across visits; started using at later visits; sometimes using across visits; stopped using at later visits; or never using across visits. General multivariable linear models evaluated most recent A1c by use category for each strategy. RESULTS: In type 1 diabetes, A1c was lower among those who starting tracking calories (-0.4%, Tukey P < .05), often counted carbs (-0.8%, Tukey P < .001), or sometimes chose low glycemic index foods (-0.5%, Tukey P = .02) vs those with less use, while participants who never drank more milk had the lowest A1c (-0.5%, Tukey P = .04). In type 2 diabetes, A1c was lower among those who often limited high fat foods (-2.0%, Tukey P = .02) or started counting carbohydrates (-1.7%, Tukey P = .07) than those who did so less. CONCLUSIONS: For several dietary strategies, more frequent use over time was related to lower A1c in youth-onset type 1 and type 2 diabetes, suggesting these strategies can likely support diabetes management for this population. Investigation into factors predicting receipt of advice for specific strategies and corresponding impact on intake might be considered.


Subject(s)
Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Diet , Glycemic Control , Adolescent , Age Factors , Blood Glucose , Child , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Feeding Behavior , Glycated Hemoglobin/metabolism , Humans , Self Report , Time Factors , United States , Young Adult
14.
Pediatr Diabetes ; 21(5): 863-870, 2020 08.
Article in English | MEDLINE | ID: mdl-32304144

ABSTRACT

AIM: Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. METHOD: We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. RESULTS: At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. CONCLUSIONS: Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.


Subject(s)
Cholesterol, LDL/blood , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Vascular Stiffness/physiology , Adolescent , Adult , Age Factors , Age of Onset , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cohort Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Angiopathies/blood , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/etiology , Diabetic Angiopathies/physiopathology , Glycated Hemoglobin/analysis , Heart Disease Risk Factors , Humans , Insulin Resistance , United States/epidemiology , Young Adult
15.
J Clin Hypertens (Greenwich) ; 22(5): 888-896, 2020 05.
Article in English | MEDLINE | ID: mdl-32297456

ABSTRACT

Central obesity may contribute to the development of hypertension in youths with diabetes. The SEARCH for Diabetes in Youth Study followed 1518 youths with type 1 diabetes (T1D) and 177 with type 2 diabetes (T2D) diagnosed when <20 years of age for incident hypertension. Incident hypertension was defined as blood pressure ≥95th percentile (or ≥130/80 mm Hg) or reporting antihypertensive therapy among those without hypertension at baseline. Poisson regression models were stratified by diabetes type and included demographic and clinical factors, clinical site, and waist-to-height ratio (WHtR). Youths with T2D were more likely to develop hypertension than those with T1D (35.6% vs 14.8%, P < .0001). For each 0.01 unit of annual increase in WHtR, adjusted relative risk for hypertension was 1.53 (95% CI 1.36-1.73) and 1.20 (95% CI 1.00-1.43) for youths with T1D and T2D, respectively. Effective strategies targeted toward reducing central obesity may reduce hypertension among youths with diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Hypertension , Adolescent , Body Mass Index , Child , Cohort Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Humans , Hypertension/epidemiology , Male , Obesity , Risk Factors , Young Adult
16.
Pediatr Diabetes ; 21(2): 349-357, 2020 03.
Article in English | MEDLINE | ID: mdl-31797506

ABSTRACT

OBJECTIVES: This study sought to: (a) assess the prevalence of diabetes complications and comorbidities screening as recommended by the American Diabetes Association (ADA) for youth and young adults (YYAs) with type 1 diabetes (T1D), (b) examine the association of previously measured metabolic status related to diabetes complications with receipt of recommended clinical screening, and (c) examine the association of satisfaction with diabetes care with receipt of recommended clinical screening. METHODS: The study included 2172 SEARCH for Diabetes in Youth participants with T1D (>10 years old, diabetes duration >5 years). Mean participant age was 17.7 ± 4.3 years with a diabetes duration of 8.1 ± 1.9 years. Linear and multinomial regression models were used to evaluate associations. RESULTS: Sixty percent of participants reported having three or more hemoglobin A1c (HbA1c) measurements in the past year. In terms of diabetes complications screening, 93% reported having blood pressure measured, 81% having an eye examination, 71% having lipid levels checked, 64% having a foot exam, and 63% completing albuminuria screening in accordance with ADA recommendations. Youth known to have worse glycemic control in the past had higher odds of not meeting HbA1c screening criteria (OR 1.11, 95% CI = 1.05, 1.17); however, after adjusting for race/ethnicity, this was no longer statistically significant. Greater satisfaction with diabetes care was associated with increased odds of meeting screening criteria for most of the ADA-recommended measures. CONCLUSIONS: Efforts should be made to improve diabetes complications screening efforts for YYAs with T1D, particularly for those at higher risk for diabetes complications.


Subject(s)
Diabetes Complications/diagnosis , Diabetes Mellitus, Type 1/complications , Mass Screening/statistics & numerical data , Registries , Adolescent , Child , Diabetes Complications/etiology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/psychology , Female , Humans , Male , Patient Satisfaction , Young Adult
17.
Ann Pediatr Endocrinol Metab ; 24(3): 187-194, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31607112

ABSTRACT

PURPOSE: Youth with type 1 diabetes mellitus (T1DM) are at risk of cardiovascular disease (CVD). We evaluated if metformin or statin use was associated with surrogate measures of improved CVD. METHODS: We included participants from the SEARCH observational study. Participants treated with insulin plus metformin (n=42) or insulin plus statin (n=39) were matched with 84 and 78 participants, respectively, treated with insulin alone. Measures of arterial stiffness obtained were pulse wave velocity (PWV), augmentation index (AI75), and heart rate variability as standard deviation of the normal-to-normal interval (SDNN) and root mean square differences of successive NN intervals (RMSSD). RESULTS: CVD measures were not significantly different among participants on insulin plus metformin versus those on insulin alone: PWV (5.9±1.0 m/sec vs. 5.8±1.5 m/sec, P=0.730), AI75 (1.8 [-6.0 to 8.0] vs. -2.4 [-10.7 to 3.8], P=0.157), SDNN (52.4 [36.8-71.1] m/sec vs. 51.8 [40.1-74.9] m/sec, P=0.592), and RMSSD (43.2 [29.4-67.6] vs. 47.4 [28.0-76.3], P=0.952). CVD measures were not different for statin users versus nonusers: PWV (5.7±0.8 m/sec vs. 5.9 ±1.1 m/sec, P=0.184), AI75 ( -4.0 [-9.5 to 1.7] vs. -6.7 [-11.3 to 5.7], P=0.998), SDNN (54.6 [43.5-77.2] m/sec vs. 63.1 [44.2-86.6] m/sec, P=0.369), and RMSSD (49.5 [31.2-74.8] vs. 59.2 [38.3-86.3], P=0.430). CONCLUSION: We found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue.

18.
Lancet Child Adolesc Health ; 3(1): 35-43, 2019 01.
Article in English | MEDLINE | ID: mdl-30409691

ABSTRACT

BACKGROUND: One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors. METHODS: This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors. FINDINGS: 1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50 000 and did not have private health insurance. INTERPRETATION: Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity. FUNDING: US Centers for Disease Control and Prevention, US National Institutes of Health.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Adolescent , Age Factors , Child , Cohort Studies , Diabetes Mellitus, Type 1/diagnosis , Female , Humans , Male , Risk Factors , Socioeconomic Factors , Young Adult
19.
Circ Cardiovasc Qual Outcomes ; 11(8): e004444, 2018 08.
Article in English | MEDLINE | ID: mdl-30354371

ABSTRACT

Background Patient-reported outcomes (PROs) are clinical tools that measure patients' goals of care and assess patient-reported physical, mental, and social well-being. Despite their value in advancing patient-centered care, routine use of PROs in stroke management has lagged. As part of the pragmatic COMPASS (Comprehensive Post-Acute Stroke Services) trial, we developed COMPASS-Care Plan (CP), a clinician-facing application that captures and analyzes PROs for stroke and transient ischemic attack patients discharged home and immediately generates individualized electronic CP. In this report, we (1) present our methods for developing and implementing COMPASS-CP PROs, (2) provide examples of CP generated from COMPASS-CP, (3) describe key functional, social, and behavioral determinants of health captured by COMPASS-CP, and (4) report on clinician experience with using COMPASS-CP in routine clinical practice for care planning and engagement of stroke and transient ischemic attack patients discharged home. Methods and Results We report on the first 871 patients enrolled in 20 North Carolina hospitals randomized to the intervention arm of COMPASS between July 2016 and February 2018; these patients completed a COMPASS follow-up visit within 14 days of hospital discharge. We also report user satisfaction results from 56 clinicians who used COMPASS-CP during these visits. COMPASS-CP identified more cognitive and depression deficits than physical deficits. Within 14-day posthospitalization, less than half of patients could list the major risk factors for stroke, 36% did not recognize blood pressure as a stroke risk factor, and 19% of patients were nonadherent with prescribed medications. Three-fourths of clinicians reported that COMPASS-CP identifies important factors impacting patients' recovery that they otherwise may have missed, and two-thirds were highly satisfied with COMPASS-CP. Conclusions The COMPASS-CP application meets an immediate need to incorporate PROs into the clinical workflow to develop patient-centered CP for stroke patients and has high user satisfaction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02588664.


Subject(s)
Algorithms , Data Mining/methods , Electronic Health Records , Ischemic Attack, Transient/therapy , Patient Reported Outcome Measures , Patient-Centered Care/methods , Stroke/therapy , Aged , Attitude of Health Personnel , Female , Health Knowledge, Attitudes, Practice , Health Status , Humans , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/physiopathology , Ischemic Attack, Transient/psychology , Male , Medication Adherence , Middle Aged , North Carolina , Patient Discharge , Patient Education as Topic , Patient Satisfaction , Risk Factors , Social Behavior , Social Determinants of Health , Stroke/diagnosis , Stroke/physiopathology , Stroke/psychology , Time Factors , Treatment Outcome
20.
Pediatr Diabetes ; 19(6): 1065-1072, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29761619

ABSTRACT

OBJECTIVE: The aim of this study was to describe recent medication patterns and changes in medication patterns and glycemic control in adolescents and young adults with incident type 2 diabetes (T2D). METHODS: Using data from the SEARCH for Diabetes in Youth Study, we conducted a cross-sectional analysis of treatments for adolescents and young adults with incident T2D in 2 periods (2002-2005 vs 2008/2012), and a longitudinal analysis of medications and glycemic control for a subset with baseline and follow-up visits. Comparisons were performed using χ2 , Fisher's exact, or ANOVA. RESULTS: Of 646 individuals in the cross-sectional analysis, a majority in each period received metformin (64.9% vs 70.4%) and/or insulin (38.1% vs 38.4%), while fewer used sulfonylureas (5.6% vs 3.6%) with non-significant changes over time. There was a significant reduction in thiazolidinedione use (5.0% vs 2.0%, P < .05). In the longitudinal analysis, 322 participants were followed for 7 years, on average. Baseline metformin users had a lower A1C (6.4% [46.7 mmol/mol]) compared to insulin (8.4% [68.2 mmol/mol], P < .001) or insulin plus any oral diabetes medication (ODM) users (7.7% [60.4 mmol/mol], P < .001). Among baseline metformin users (n = 138), 29.7% reported metformin at follow-up, with the remainder adding (19.6%) or switching to insulin (8.0%), ODM (15.9%), or lifestyle only (26.8%). Of those receiving insulin (±ODM) (n = 129), 76% reported insulin use at follow-up. Overall, 35% were at A1C goal (<7.0%, 53 mmol/mol) at follow-up. CONCLUSIONS: Youth-onset T2D is still largely being treated with metformin and/or insulin. The majority treated were not at American Diabetes Association (ADA)-recommended goal 7 years after diagnosis.

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