Jeanette M. Stafford

Trends in the Prevalence of Ketoacidosis at Diabetes Diagnosis: The SEARCH for Diabetes in Youth Study

OBJECTIVE: To estimate temporal changes in the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 or type 2 diabetes in youth and to explore factors associated with its occurrence. METHODS: Five centers identified incident cases of diabetes among youth aged 0 to 19 years starting in 2002. DKA presence was defined as a bicarbonate level <15 mmol/L and/or a pH <7.25 (venous) or <7.30 (arterial or capillary) or mention of DKA in the medical records. We assessed trends in the prevalence of DKA over 3 time periods (2002–2003, 2004–2005, and 2008–2010). Logistic regression was used to determine factors associated with DKA. RESULTS: In youth with type 1 diabetes (n = 5615), the prevalence of DKA was high and stable over time (30.2% in 2002–2003, 29.1% in 2004–2005, and 31.1% in 2008–2010; P for trend = .42). Higher prevalence was associated with younger age at diagnosis (P < .0001), minority race/ethnicity (P = .019), income (P = .019), and lack of private health insurance (P = 008). Among youth with type 2 diabetes (n = 1425), DKA prevalence decreased from 11.7% in 2002–2003 to 5.7% in 2008–2010 (P for trend = .005). Higher prevalence was associated with younger age at diagnosis (P = .001), minority race/ethnicity (P = .013), and male gender (P = .001). CONCLUSIONS: The frequency of DKA in youth with type 1 diabetes, although stable, remains high, indicating a persistent need for increased awareness of signs and symptoms of diabetes and better access to health care. In youth with type 2 diabetes, DKA at onset is less common and is decreasing over time.

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure–associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein–protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure–associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood

Importance The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown. Objective To determine the prevalence of and risk factors for complications related to type 1 diabetes vs type 2 diabetes among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence. Design, Setting, and Participants Observational study from 2002 to 2015 in 5 US locations, including 2018 participants with type 1 and type 2 diabetes diagnosed at younger than 20 years, with single outcome measures between 2011 and 2015. Exposures Type 1 and type 2 diabetes and established risk factors (hemoglobin A1c level, body mass index, waist-height ratio, and mean arterial blood pressure). Main Outcomes and Measures Diabetic kidney disease, retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension. Results Of 2018 participants, 1746 had type 1 diabetes (mean age, 17.9 years [SD, 4.1]; 1327 non-Hispanic white [76.0%]; 867 female patients [49.7%]), and 272 had type 2 (mean age, 22.1 years [SD, 3.5]; 72 non-Hispanic white [26.5%]; 181 female patients [66.5%]). Mean diabetes duration was 7.9 years (both groups). Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence of diabetic kidney disease (19.9% vs 5.8%; absolute difference [AD], 14.0%; 95% CI, 9.1%-19.9%; P < .001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; P = .02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; P < .001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; P < .001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; P < .001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, –3.1% to 6.5; P = .62). After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease (odds ratio [OR], 2.58; 95% CI, 1.39-4.81; P=.003), retinopathy (OR, 2.24; 95% CI, 1.11-4.50; P = .02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; P = .001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; P = .80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; P = .55). Conclusions and Relevance Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1, but frequent in both groups. These findings support early monitoring of youth with diabetes for development of complications.

Diabetes Foot Self-care Practices in a Rural, Triethnic Population

Purpose The purposes of this study were to assess the level of foot self-care performed in a rural, multiethnic population of older adults and to identify factors associated with foot self-care. Methods The Evaluating Long-term Diabetes Self-management Among Elder Rural Adults study included a random sample of 701 African American, Native American, and white adults from 2 rural North Carolina counties. Participants completed in-home interviews, 5 foot selfcare practices from the Summary of Diabetes Self-Care Activities (SDSCA), functional status measures, and measures of education and support for foot care. Results Foot care practices/behaviors reported at least 6 days/week ranged from 35.6% for inspecting shoes to 79.2% for not soaking feet. Four independent predictors of the SDSCA summary foot care index score were observed: having been shown how to care for feet (P< .0001), female gender (P= .03), having had a doctor check nerves in feet in past year (P= .02), and not receiving support caring for feet (P = .0425). Conclusions These findings indicate that educating patients about foot self-care may encourage routine foot care but that those dependent on either formal or informal support to perform foot care do so less frequently than those who perform it independently.

Clinical utility of the resistive index in atherosclerotic renovascular disease

OBJECTIVE This retrospective study examines the relationship between the renal resistive index (RI) and blood pressure and renal function response after open and percutaneous intervention for atherosclerotic renovascular disease (AS-RVD). METHODS From March 1997 to December 2005, 86 patients (46 women, 40 men; mean age, 68 +/- 10 years) underwent renal duplex sonography (RDS), including main renal artery and hilar vessel Doppler interrogation, before treatment of AS-RVD. Of these, 56 patients had open operative repair, and 30 had percutaneous intervention. The RI (1-[EDV/PSV]) was calculated from the kidney with the highest peak systolic velocity (PSV). Hypertension response was graded from preprocedural and postprocedural blood pressure measurements and medication requirements. Renal function response was graded by a >or=20% change in estimated glomerular filtration rate (eGFR) calculated from the serum creatinine concentration. RESULTS Comorbid conditions, baseline blood pressure, and preoperative renal function were not significantly different between open and percutaneous groups. Baseline characteristics that differed between the percutaneous vs open group were higher mean age (71 +/- 11 years vs 67 +/- 9 years; P = .05), kidney length (11.3 +/- 1.3 cm vs 10.7 +/- 1.2 cm; P = .02), proportion of patients with RI >or=0.8 (50% vs 21%; P = .01), and proportion of bilateral AS-RVD (37% vs 80%; P < .01). After controlling for preintervention blood pressure and extent of repair, postoperative eGFR differed significantly for RI <0.8 or >or=0.8 when all patients (P = .003) and percutaneous intervention (P = .008) were considered. Specifically, eGFR declined from preprocedure to postprocedure in the patients with RI >or=0.8 after percutaneous repair and in the group analyzed as a whole. Neither systolic nor diastolic pressure after intervention demonstrated an association with RI. Considering all patients and both groups, multivariable proportional hazards regression models demonstrated that RI was predictive of all-cause mortality. RI was the most powerful predictor of death during follow-up (hazard ratio, 6.7; 95% confidence interval, 2.6-17.2; P < .001). CONCLUSION After intervention for AS-RVD, RI was associated with renal function, but not blood pressure response. A strong, independent relationship between RI and mortality was observed for all patients and both treatment groups.

Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10−9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10−4). The strongest combined association was at rs1823125 (P=1.5 × 10−10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10−9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10−4). The strongest combined association was at rs1823125 (P=1.5 × 10−10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Results of surgical management of acute thromboembolic lower extremity ischemia

OBJECTIVE Acute lower extremity ischemia secondary to arterial thromboembolism is a common problem. Contemporary data regarding this problem are sparse. This report examines a 10-year single-center experience and describes the surgical management and outcomes observed. METHODS Procedural codes were used to identify consecutive patients treated surgically for acute lower extremity embolization from January 2002 to September 2012. Patients presenting >7 days after onset of symptoms, occlusion of grafts/stents, and cases secondary to trauma or iatrogenic injury were excluded. Data collected included demographics, medical comorbidities, presenting clinical characteristics, procedural specifics, and postoperative outcomes. Results were evaluated using descriptive statistics, product-limit survival analysis, and logistic regression multivariable modeling. RESULTS The study sample included 170 patients (47% female). Mean age was 69.1 ± 16.0 years. Of these, 82 patients (49%) had a previous history of atrial fibrillation, and four (2%) were therapeutically anticoagulated (international normalized ratio ≥2.0) at presentation. Presentation for 83% was >6 hours after symptom onset, and 9% presented with a concurrent acute stroke. Femoral artery exploration with embolectomy was the most common procedural management and was used for aortic, iliac, and infrainguinal occlusion. Ten patients (6%) required bypass for limb salvage during the initial operation. Local instillation of thrombolytic agents as an adjunct to embolectomy was used in 16%, fasciotomies were performed in 39%, and unexpected return to the operating room occurred in 24%. Ninety-day amputation above or below the knee was required during the index hospitalization in 26 patients (15%). In-hospital or 30-day mortality was 18%. Median (interquartile range) length of stay was 8 days (4, 16 days), and 36% of patients were discharged to a nursing facility. Recurrent extremity embolization occurred in 23 patients (14%) at a median interval of 1.6 months. The 5-year amputation freedom and survival estimates were 80% and 41%, respectively. Predictors of 90-day amputation included prior vascular surgery, gangrene, and fasciotomy. Predictors of 30-day mortality included age, history of coronary artery disease, prior vascular surgery, and concurrent stroke. CONCLUSIONS Despite advances in contemporary medical care, lower extremity arterial embolization remains a condition that is associated with significant morbidity and mortality. Furthermore, the condition is resource-intensive to treat and is likely preventable (initially or in recurrence) in a substantial subset of patients.

Endovascular management of atherosclerotic renovascular disease: early results following primary intervention.

OBJECTIVE This retrospective review examines periprocedural morbidity and early functional responses to primary renal artery angioplasty and stenting (RA-PTAS) for patients with atherosclerotic renovascular disease (RVD). METHODS Consecutive patients undergoing primary RA-PTAS for hemodynamically significant atherosclerotic RVD with hypertension and/or ischemic nephropathy were identified from a prospectively maintained registry. Hypertension responses were determined based on pre- and post-intervention blood pressure measurements and medication requirements. Estimated glomerular filtration rate (eGFR) was used to determine renal function responses. Both hypertension and renal function responses were assessed at least three weeks after RA-PTAS. Stepwise multivariable regression analysis was used to examine associations between blood pressure and renal function responses to RA-PTAS and select clinical variables. RESULTS One-hundred ten primary RA-PTAS were performed on 99 patients with atherosclerotic RVD with a mean angiographic diameter-reducing stenosis of 79.2 +/- 12.9%. All patients had hypertension (mean of 3.4 +/- 1.3 antihypertensive agents). Mean pre-intervention eGFR was 49.9 +/- 22.7 mL/min/1.73 m(2), and 74 patients had a pre-intervention eGFR < 60 mL/min/1.73 m(2). The technical success rate for RA-PTAS was 94.5%. The periprocedural complication rate was 5.5%; there were no periprocedural deaths. Statistically significant decreases in mean systolic blood pressure (161.3 +/- 25.2 vs. 148.5 +/- 25.2 post-intervention, P < .0001), diastolic blood pressure (78.6 +/- 13.3 versus 72.5 +/- 13.5 post-intervention, P < .0001), and number of antihypertensive agents (3.3 +/- 1.2 versus 3.1+/- 1.3 post-intervention, P = .009) were observed. Assessed categorically, hypertension response to RA-PTAS was cured in 1.1%, improved in 20.5%, and unchanged in 78.4%. Categorical eGFR response to RA-PTAS was improved in 27.7%, unchanged in 65.1%, and worsened in 7.2%. Multivariable stepwise regression revealed associations between pre- and post-intervention systolic blood pressure (P < .0001), diastolic blood pressure (P < .0001), and eGFR (P < .0001), as well as a trend toward improved diastolic blood pressure response among patients managed with staged bilateral intervention (P = .0589). CONCLUSION Primary RA-PTAS for atherosclerotic RVD was associated with low peri-procedural morbidity and mortality but only modest early improvements in blood pressure and renal function. Results from ongoing prospective trials are needed to assess the long term outcomes associated with RA-PTAS and clarify its role in the management of atherosclerotic RVD.

Complementary and Alternative Medicine Use and Diabetes Self-Management Among Rural Older Adults

Complementary and alternative medicine (CAM) is a growing form of self-care and is related to other healthy behaviors. This study examines the relationship between CAM use and diabetes self-management. A survey of rural older African American, Native American, and White adults with diabetes was conducted. Data were collected on diabetes self-management domains and general and diabetes-specific CAM use. Some associations were observed, particularly for CAM use and following a healthy eating plan. CAM is part of the health maintenance strategy of rural older adults with diabetes. Further research should examine the health trajectory associated with CAM use in this population.