Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function. METHODS: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy. RESULTS: Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR (p=0.007), lower 24 h serum melatonin output (p=0.042) and greater day-to-day sleep variability (p=0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels (r=0.555, p=0.007). CONCLUSIONS/INTERPRETATION: ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy.

Plasma undercarboxylated osteocalcin dynamics with glycemic stress reflects insulin sensitivity and beta-cell function in humans with and without T2DM.

This study aimed to better understand the relationship between bone-related biomarkers and nutrient stress in the context of metabolic health. We investigated plasma osteocalcin (OC) during an oral glucose challenge and experimental hyperinsulinemia in Type 2 diabetes (T2DM) and lean healthy controls (LHC). Older individuals with obesity and T2DM (n = 9) and young LHCs (n = 9) underwent a 75g oral glucose tolerance test (OGTT) and a 40 mU/m2/min hyperinsulinemic-euglycemic clamp. Plasma undercarboxylated OC (ucOC) and total OC were measured at baseline, 60mins, and 120mins of the OGTT and clamp via ELISA. In addition, plasma alkaline phosphatase (ALP), leptin, adiponectin, Vitamin D and insulin were measured and indices of insulin sensitivity and ß-cell function were derived. The T2DM group had lower (p<0.05) ucOC and ucOC:total OC ratio than LHC during both the OGTT and clamp. Further, baseline ucOC was positively correlated to indices of ß-cell function and negatively correlated to indices of insulin resistance when both groups were combined (all p<0.05). Suppression of OC observed in T2DM may be related to glucose intolerance and insulin resistance. Similarly, our data suggest that the observed phenotypic differences between groups are likely a product of long-term glucose dysregulation rather than acute flux in glucose or insulin.

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.3 years, 54.3% female) who were not shift-workers participated. The presence of diabetic retinopathy was determined. The standard deviation of sleep duration and sleep midpoint across all recorded nights were used to quantify sleep variability and regularity, respectively, assessed by 14-day actigraphy. The presence and severity of sleep apnea were assessed using an overnight home monitor. Low-density lipoprotein, haemoglobin A1C and high-sensitivity C-reactive protein were collected. Multiple regression analysis using natural-log-transformed values was performed to establish an independent association between sleep variability and high-sensitivity C-reactive protein. Twenty-two (62.9%) patients had diabetic retinopathy. The median (interquartile range) of high-sensitivity C-reactive protein was 2.4 (1.4, 4.6) mg L-1 . Higher sleep variability was significantly associated with higher high-sensitivity C-reactive protein (r = 0.342, p = 0.044), as was haemoglobin A1C (r = 0.431, p = 0.010) and low-density lipoprotein (r = 0.379, p = 0.025), but not sleep regularity, sleep apnea severity or diabetic retinopathy. Multiple regression analysis showed that higher sleep variability (B = 0.907, p = 0.038) and higher HbA1c (B = 1.519, p = 0.035), but not low-density lipoprotein, contributed to higher high-sensitivity C-reactive protein. In conclusion, higher sleep variability in patients with type 2 diabetes who were not shift-workers was independently associated with higher systemic inflammation, conferring increased cardiovascular risk. Whether sleep interventions to reduce sleep variability can reduce systemic inflammation and improve cardiometabolic health should be investigated.

Diet, Gut Microbiome, and Their End Metabolites Associate With Acute Pancreatitis Risk.

INTRODUCTION: Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome, and their impact on microbial end metabolites have not been studied in AP. We aimed to determine differences in (i) dietary intake (ii) gut microbiome diversity and sulfidogenic bacterial abundance, and (iii) serum short-chain fatty acid (SCFA) and hydrogen sulfide (H 2 S) concentrations in AP and control subjects. METHODS: This case-control study recruited 54 AP and 46 control subjects during hospitalization. Clinical and diet data and stool and blood samples were collected. 16S rDNA sequencing was used to determine gut microbiome alpha diversity and composition. Serum SCFA and H 2 S levels were measured. Machine learning (ML) model was used to identify microbial targets associated with AP. RESULTS: AP patients had a decreased intake of vitamin D 3 , whole grains, fish, and beneficial eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. AP patients also had lower gut microbiome diversity ( P = 0.021) and a higher abundance of sulfidogenic bacteria including Veillonella sp. and Haemophilus sp., which were associated with AP risk. Serum acetate and H 2 S concentrations were significantly higher in the AP group ( P < 0.001 and P = 0.043, respectively). ML model had 96% predictive ability to distinguish AP patients from controls. DISCUSSION: AP patients have decreased beneficial nutrient intake and gut microbiome diversity. An increased abundance of H 2 S-producing genera in the AP and SCFA-producing genera in the control group and predictive ability of ML model to distinguish AP patients indicates that diet, gut microbiota, and their end metabolites play a key role in AP.

Prevalence of Undiagnosed Diabetes Identified by a Novel Electronic Medical Record Diabetes Screening Program in an Urban Emergency Department in the US.

This cross-sectional study describes a screening program that was developed to screen for type 2 diabetes in an urban emergency department setting in the US.

Stress and human health in diabetes: A report from the 19th Chicago Biomedical Consortium symposium.

Stress and diabetes coexist in a vicious cycle. Different types of stress lead to diabetes, while diabetes itself is a major life stressor. This was the focus of the Chicago Biomedical Consortium's 19th annual symposium, "Stress and Human Health: Diabetes," in November 2022. There, researchers primarily from the Chicago area met to explore how different sources of stress - from the cells to the community - impact diabetes outcomes. Presenters discussed the consequences of stress arising from mutant proteins, obesity, sleep disturbances, environmental pollutants, COVID-19, and racial and socioeconomic disparities. This symposium showcased the latest diabetes research and highlighted promising new treatment approaches for mitigating stress in diabetes.

Assessing the Pathophysiology of Hyperglycemia in the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: From the Type 1 Diabetes in Acute Pancreatitis Consortium.

OBJECTIVES: The metabolic abnormalities that lead to diabetes mellitus (DM) after an episode of acute pancreatitis (AP) have not been extensively studied. This article describes the objectives, hypotheses, and methods of mechanistic studies of glucose metabolism that comprise secondary outcomes of the DREAM (Diabetes RElated to Acute pancreatitis and its Mechanisms) Study. METHODS: Three months after an index episode of AP, participants without preexisting DM will undergo baseline testing with an oral glucose tolerance test. Participants will be followed longitudinally in three subcohorts with distinct metabolic tests. In the first and largest subcohort, oral glucose tolerance tests will be repeated 12 months after AP and annually to assess changes in ß-cell function, insulin secretion, and insulin sensitivity. In the second, mixed meal tolerance tests will be performed at 3 and 12 months, then annually, and following incident DM to assess incretin and pancreatic polypeptide responses. In the third, frequently sampled intravenous glucose tolerance tests will be performed at 3 months and 12 months to assess the first-phase insulin response and more precisely measure ß-cell function and insulin sensitivity. CONCLUSIONS: The DREAM study will comprehensively assess the metabolic and endocrine changes that precede and lead to the development of DM after AP.

Effects of Sleep-Extend on glucose metabolism in women with a history of gestational diabetes: a pilot randomized trial.

OBJECTIVES: Women with a history of gestational diabetes (GDM) are at 7-fold increase in the risk of developing diabetes. Insufficient sleep has also been shown to increase diabetes risk. This study aimed to explore the feasibility of a sleep extension in women with a history of GDM and short sleep, and effects on glucose metabolism. METHODS: Women age 18-45 years with a history of GDM and actigraphy confirmed short sleep duration (<7 h/night) on weekdays were randomized at a ratio of 1 control (heathy living information) to 2 cases (6 weeks of "Sleep-Extend" intervention: use of a Fitbit, weekly digital content, and weekly coaching to increase sleep duration). An oral glucose tolerance test (OGTT), 7-day actigraphy recording, and questionnaires were obtained at baseline and 6 weeks. Mean differences between baseline and end-of-intervention parameters were compared using independent samples t-tests. RESULTS: Mean (SD) sleep duration increased within the Sleep-Extend group (n=9, +26.9 (42.5) min) but decreased within the controls (n=5, - 9.1 (20.4) min), a mean difference (MD) of 35.9 min (95% confidence interval (CI) - 8.6, 80.5). Fasting glucose increased, but less in Sleep-Extend vs. control groups (1.6 (9.4) vs 10.4 (8.2) mg/dL, MD - 8.8 mg/dL (95% CI - 19.8, 2.1), while 2-h glucose levels after an OGTT did not differ. Compared to controls, Sleep-Extend had decreased fatigue score (MD - 10.6, 95%CI - 20.7, - 0.6), and increased self-report physical activity (MD 5036 MET- minutes/week, 95%CI 343, 9729. Fitbit compliance and satisfaction in Sleep-Extend group was high. CONCLUSION: Sleep extension is feasible in women with a history of GDM, with benefits in fatigue and physical activity, and possibly glucose metabolism. These data support a larger study exploring benefits of sleep extension on glucose metabolism in these high-risk women. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03638102 (8/20/2018).

Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea.

STUDY OBJECTIVES: To explore the association of continuous positive airway pressure (CPAP) adherence with clinical outcomes in patients with type 2 diabetes and obstructive sleep apnea in a real-world setting. METHODS: This was a retrospective study of patients with type 2 diabetes diagnosed with obstructive sleep apnea between 2010 and 2017. CPAP adherence (usage for ≥ 4 h/night for ≥ 70% of nights) was determined from the first CPAP report following the polysomnography. Data including estimated glomerular filtration rate, hemoglobin A1c, systolic and diastolic blood pressure, lipid panel, and incident cardiovascular/peripheral vascular/cerebrovascular events were extracted from medical records. Mixed-effects linear regression modeling of longitudinal repeated measures within patients was utilized for continuous outcomes, and logistic regression modeling was used for binary outcomes. Models were controlled for age, sex, body mass index, medications, and baseline levels of outcomes. RESULTS: Of the 1,295 patients, 260 (20.7%) were CPAP adherent, 318 (24.5%) were CPAP nonadherent, and 717 (55.3%) had insufficient data. The follow-up period was, on average, 2.5 (1.7) years. Compared to those who were CPAP nonadherent, those who were adherent had a significantly lower systolic blood pressure (ß = -1.95 mm Hg, P = .001) and diastolic blood pressure (ß = -2.33 mm Hg, P < .0001). Among the patients who were CPAP adherent, a 17% greater CPAP adherence was associated with a 2 mm Hg lower systolic blood pressure. Lipids, hemoglobin A1c, estimated glomerular filtration rate, and incident cardiovascular/peripheral vascular/cerebrovascular events were not different between the 2 groups. CONCLUSIONS: Achieving CPAP adherence in patients with type 2 diabetes and obstructive sleep apnea was associated with significantly lower blood pressure. Greater CPAP use within patients who were adherent was associated with lower systolic blood pressure. CITATION: Sheth U, Monson RS, Prasad B, et al. Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):1563-1569.

Child and Caregiver Perspectives Towards Facial Appearance in Children With Microtia With or Without Craniofacial Microsomia Using a Newly Developed Likert Scale.

Craniofacial microsomia (CFM) is the second most common congenital craniofacial malformation characterized by asymmetric malformation of the ear and mandible. Numerous studies have reported the importance of child perspective and psychosocial issues in patients with craniofacial abnormalities. However, clinical tools to evaluate child and caregiver perspectives in patients with microtia with or without CFM have been limited or not reported in the literature. The authors aimed to (1) To develop a tool for measuring patient and caregiver evaluation of facial appearance as it relates to microtia and craniofacial microsomia (CFM). (2) To utilize this tool in comparing children, between 7 and 20 years of age, and caregiver perspectives towards facial appearance in patients with microtia with or without craniofacial microsomia (CFM). A prospective single center study conducted from 2016 to 2017 using newly developed 13-item (Microtia) and 27-item (CFM) 5-point Likert scale Likert scale questionnaires given to patients with CFM and caregivers at a craniofacial center. Aged 7 to 20 (N = 25) and their caregivers. A total of 25 patients (13 male, 12 female; mean age at time of survey 13.2 ±â€Š3.7) met criteria for the study. The Likert scale developed and presented in this study may be a useful tool for clinical use in investigating patient and caregiver perspectives for planning surgical timeline. Based on our pilot data it is important to incorporate all voices into decision-making on timing.

Relationship between Intrinsically Photosensitive Ganglion Cell Function and Circadian Regulation in Diabetic Retinopathy.

BACKGROUND: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control non-visual light responses (e.g. pupillary light reflex and circadian entrainment). Patients with diabetic retinopathy (DR) show reduced ipRGC function, as inferred by abnormalities in the post illumination pupil response (PIPR). We explored whether ipRGC function in DR is associated with circadian outputs and sleep/wake behavior. METHODS: Forty-five participants (15 without diabetes, 15 with type 2 diabetes (T2D) and no DR, 15 with T2D and DR) participated. ipRGC function was inferred from the PIPR (pupil size following stimulus offset). Circadian outputs were melatonin amplitude (overnight urinary 6-sulfatoxymelatonin (aMT6s)) and timing (dim light melatonin onset (DLMO)), and evening salivary cortisol levels. Sleep/wake patterns were measured with wrist actigraphy and insomnia symptoms were assessed subjectively. RESULTS: Patients with T2D and DR had smaller PIPR and lower urinary aMT6s than other groups (p < 0.001). In adjusted regression models, smaller PIPR was associated with lower urinary aMT6s (ß = 4.552, p = 0.005). Patients with DR were more likely to have no detectable DLMO (p = 0.049), higher evening salivary cortisol, greater insomnia symptoms and greater sleep variability compared to other groups. Sleep duration, efficiency and rest-activity rhythms were similar. CONCLUSION: Reduced ipRGC function in DR is associated with circadian dysregulation and sleep disturbances, although a causal relationship cannot be established in this cross-sectional study. Prospective mechanistic and intervention studies examining circadian and sleep health in these patients are warranted.

Factors Associated with Weight Loss After Metabolic Surgery in a Multiethnic Sample of 1012 Patients.

BACKGROUND: Metabolic surgery is the most effective method for weight loss in the long-term treatment of morbid obesity and its comorbidities. The primary aim of this study was to examine factors associated with percent total weight loss (%TWL) after metabolic surgery among an ethnically diverse sample of patients. METHODS: A retrospective review was performed on 1012 patients who underwent either a sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) at our institution between January 2008 and June 2015. RESULTS: African Americans had a lower %TWL than non-Hispanic/Latino Whites at 6, 9, 12, 18, and 48 months. At all timeframes, there was a negative association between pre-surgery TWL and %TWL after surgery. Female sex was negatively associated with %TWL at 3 months only. Higher initial BMI was also associated with greater post-operative %TWL at 18, 24 and 36 months. Older patients had lower %TWL at 6, 9, 12 and 24 months post-surgery. Patients who received RYGB had greater %TWL than those who received SG at 3, 6, 9, 12, 24 and 36 months. CONCLUSIONS: African Americans had a lower %TWL than non-Hispanic/Latino Whites at most time points; there were no other significant race/ethnicity or sex differences. BMI (greater initial BMI), age (lower) and RYGB were associated with a greater post-operative %TWL at certain post-surgery follow-up time points. A limitation of this study is that there was missing data at a number of time points due to lack of attendance at certain follow-up visits.

Delay in Cleft Lip and Palate Surgical Repair: An Institutional Review on Cleft Health Disparities in an Urban Population.

Access to specialized medical care is critical to decrease complications and minimize long-term morbidity, yet racial disparities in cleft surgery persist as time to initial reconstruction remains delayed among minority patients. Research has demonstrated an average 3-week delay in surgery for minority patients nationally. A retrospective chart review of patient demographics, visit timing, and surgical history was performed for patients who underwent primary cleft lip with or without palate (CL + P) reconstruction between 2002 and 2016 at an urban craniofacial center. Of the 89 children who underwent surgery, 87% were ethnic minorities (58% Hispanic, 25% African-American, 4% Asian/Other). Caucasian children were the earliest to receive CL (3.5 months) and CP (13-months) repair. Minority children trended toward a delay in CL repair, with surgery for African-Americans at 5-months (P = 0.06) and Hispanics at 4.8-months (P = 0.07). Time from first visit to CL surgery showed significant delays for minority, non-English speaking, and public insurance patients; however, for CP repair, male children were delayed from first visit to surgery compared to females (P = 0.03). While there was no statistical difference in age at CL or CP surgical repair among our racial/ethnic cohorts, there were significant racial/ethnic differences in timing spent in the preoperative period for CL. However, racial/ethnic differences decreased as the patients spent more time within the healthcare system. Thus, established, interdisciplinary cleft/craniofacial centers well versed in minority patients can minimize the complex social and cultural factors that contribute to delays in cleft care.

Robotic Adrenalectomy: Are We Expanding the Indications of Minimally Invasive Surgery?

INTRODUCTION: Laparoscopic adrenalectomy (LA) is accepted as the gold standard treatment for most adrenal pathologies. Open surgery is still considered the standard of care for large tumors and malignancies. In the past decade, robotic adrenalectomy (RA) has become an alternative to the laparoscopic and open approaches. The aim of this study was to analyze perioperative and postoperative outcomes in a series of consecutive nonselected patients undergoing a RA, to determine whether factors that negatively affect outcomes in LA (body mass index [BMI], size, and side of the tumor) have the same impact in RA. MATERIALS AND METHODS: This is a single-center single-surgeon retrospective study with 43 patients who underwent a RA. Patients were divided into different groups according to tumor size (cutoff values of 5 or 8 cm), tumor side (left/right), and BMI (cutoff value of kg/m2). Perioperative and postoperative outcomes included operative time, length of hospital stay, blood loss, readmissions, complications, and conversions to open. RESULTS: There were no significant differences between the groups with tumors <5 cm versus ≥5 cm regarding gender, age, race, BMI, American Society of Anesthesiologists (ASA) score, history of previous abdominal surgery, tumor side, and histopathological diagnosis (all P values ≥.06). There were no significant differences in any of the outcomes analyzed with respect to the tumor size (all P values ≥.14) except for a higher occurrence of complications in patients with tumors ≥8 cm versus <8 cm (P = .03). There were no significant differences in any outcomes related to side (left versus right) of the tumor nor BMI (<30 versus ≥30 kg/m2). The overall readmission and conversion rates were both 2.3% and no mortalities were registered. CONCLUSION: Patient's BMI, tumor side, and size did not demonstrate a negative impact on perioperative and postoperative outcomes of RA. This approach could potentially expand the indications of minimally invasive surgery.

Over ten-year insulin independence following single allogeneic islet transplant without T-cell depleting antibody induction.

Islet cell transplantation is a promising functional cure for type 1 diabetes; however, maintaining long-term islet graft function and insulin independence is difficult to achieve. In this short report we present a patient with situs inversus, who at the time of islet transplantation had a 26-year history of type 1 diabetes, complicated by hypoglycemic unawareness and severe hypoglycemic events. After a single allogeneic islet transplant of a low islet mass, and despite developing de novo anti-insulin and anti-GAD65 autoantibodies, the patient has remarkably maintained insulin independence with tight glycemic control and normal metabolic profiles for 10 years, after receiving prolonged non-T-cell depleting immunosuppression.

Concerns and hopes of patients with type 1 diabetes prior to islet cell transplantation: A content analysis.

AIMS: Islet cell transplantation can functionally cure type 1 diabetes complicated by hypoglycemia unawareness (HU), but requires immunosuppression. This study identified the lived experiences and risk/benefit considerations of patients pre-transplant. METHODS: Content analysis identified themes from four open-ended questions pre-transplant in an islet transplant clinical trial. The sample included 23 (19 female) patients, with a mean age = 48.3 and diabetes duration = 29.3 years. RESULTS: Lack of control due to diabetes and HU was the overarching theme pre-transplant. Four sub-themes were also identified: fear of hypoglycemia, diabetes-related complications, hopes/expectations after transplant, and transplant outcomes. Patients expressed fear of HU and long-term complications pre-transplant, and hoped islet transplant would improve diabetes management. Patients further emphasized anxiety over burdening others, and hopes of advancing research. In addition, other patients emphasized frustrations regarding the impact of HU on themselves, such as the inability to perform activities of daily living. Many patients were primarily worried about immunosuppressive side effects rather than islet transplant success. CONCLUSIONS: Patients viewed islet transplantation as a means to gain autonomy and control over their lives. They desired reduced anxiety associated with HU, despite concerns over immunosuppressive side-effects. These findings need confirmation, but may help to further improve patient education and patient-provider communication.

Long term (4 years) improved insulin sensitivity following islet cell transplant in type 1 diabetes.

BACKGROUND: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). Insulin sensitivity improves shortly after islet cell transplant for T1D, yet long-term changes in IS and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. METHODS: Up to 9 years (mean 4) of longitudinal data were available on 22 adults (18 female) with T1D who received 1 to 3 transplants in Phase 1/2 or 3 clinical trials (2004-2014). Metabolic testing posttransplant estimated IS by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR; 111 observations) and the Simple Index of Insulin Sensitivity (SIis ; 95 observations). RESULTS: Simple Index of Insulin Sensitivity significantly increased the first year posttransplant (P = .02), then stabilized (P = .39); HOMA-IR remained stable posttransplant (P = .92). Adjusting for age and BMI, higher SIis was associated with lower HbA1c following transplant (P = .03). Greater IS as measured by lower HOMA-IR and higher SIis was associated with lower fasting C-peptide (both P ≤ .04) and also with higher exenatide dose (both P ≤ .01). More islets transplanted were associated with higher SIis (P < .0001). Lower leptin at transplant predicted lower HOMA-IR and higher SIis after transplant, and lower bone marker receptor activator of nuclear factor kappa-B ligand predicted lower HOMA-IR (all P ≤ .01). CONCLUSIONS: Insulin sensitivity measured by SIis was improved several years following transplant, while IS measured by HOMA-IR did not worsen. Higher exenatide dose, more islets transplanted, and diet and exercise (lowering leptin and receptor activator of nuclear factor kappa-B ligand) may improve IS, which may enhance glycaemic control and lower metabolic demand on transplanted islets. Long-term clamp studies are needed to confirm these results.

Coronary artery calcium may stabilize following islet cell transplantation in patients with type 1 diabetes.

Islet cell transplantation can functionally cure type 1 diabetes and also improve carotid intima-media thickness. This study provides a preliminary description of changes in coronary artery calcium following islet transplantation, and associated factors. Coronary artery calcium was measured in 14 patients with type 1 diabetes (11 had measures both pre- and post-transplant [mean 2.3 years]) in the University of Illinois at Chicago's clinical trial. Multivariable mixed-effects linear regression of repeated measures was used to quantify calcium change and determine if this change was longitudinally associated with risk/protective factors. Thirteen of the patients were female, with mean baseline age, diabetes duration, and BMI of 47.6 and 28.7 years, and 23.1, respectively. Over half (57%) had detectable coronary artery calcium pre-transplant. Minimal change (0.39 mm3 /y, P = .02) occurred in coronary artery calcium levels pre- to post-transplant. No patient met criteria for calcium progression. Coronary artery calcium was positively associated with total and small VLDL particles (P ≤ .02), statin dose (P = .02), and urine albumin-to-creatinine ratio (P = .04) and negatively associated with free fatty acids (P = .03), total HDL (P = .03), large HDL particles (P = .005), and tacrolimus dose (P = .02). Islet transplant may stabilize coronary artery calcium, with optimal management of lipids and kidney function remaining key therapeutic targets. [NCT00679041].

Oestradiol levels may differ between premenopausal women, ages 18-50, with type 1 diabetes and matched controls.

BACKGROUND: This study aimed to investigate whether oestradiol differs between premenopausal women with and without type 1 diabetes and whether levels are associated with such factors as age, reproductive history or diabetes management. METHODS: Oestradiol in premenopausal women with type 1 diabetes (n = 89; age = 18-50 years; duration = 13-18 years) and age-matched/race-matched controls without diabetes (n = 76) was collected during a cross-sectional ancillary study of the Wisconsin Diabetes Registry Study, a population-based incident cohort. Total and bioavailable oestradiol and sex hormone-binding globulin were compared using multivariable regression (e.g. adjusting for reproductive history). RESULTS: Adjusted mean total and bioavailable oestradiol did not differ overall by diabetes status (p ≥ 0.74), while adjusted mean sex hormone-binding globulin was higher in type 1 diabetes women (p = 0.02). However, only in women with type 1 diabetes and not controls (interaction p = 0.0005) was total oestradiol positively associated with the duration of reproductive years with unsuppressed ovarian function (UnsuppOvFx = years since menarche minus years on hormonal contraceptives/pregnant/breastfeeding). When stratified into less than/equal to or greater than the median 9 years' duration of UnsuppOvFx, compared with controls, women with type 1 diabetes had significantly lower total oestradiol in the ≤9 years group [ß = -43.2 pg mL-1 (-158.6 pmol L-1 ), p = 0.04] and significantly higher total oestradiol in the >9 years group [ß = 53.9 pg mL-1 (197.9 pmol L-1 ), p = 0.04]. Results remained consistent during additional statistical adjustments and sensitivity analyses. CONCLUSIONS: Compared with controls, women with type 1 diabetes may have lower oestradiol when they have a shorter duration of UnsuppOvFx and higher oestradiol when they have a longer duration of UnsuppOvFx. Given the potential effects of insulin on ovarian function, oestradiol production may vary across the lifespan for women with type 1 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

Trends in Breast Reconstruction by Ethnicity: An Institutional Review Centered on the Treatment of an Urban Population.

Previous studies have investigated reconstructive decisions after mastectomy and such studies document a preference among African American women for autologous tissue-based procedures and among Latin American women for implant-based reconstructions, however, there is a paucity of studies evaluating the current relationship between ethnicity and reconstructive preferences. This institutional review provides a unique, up-to-date evaluation of an understudied urban population composed of majority ethnic minority patients and explores reconstructive trends. Consecutive breast reconstruction patients were entered into a prospectively maintained database at the University of Illinois at Chicago and affiliate hospitals between July 2010 and October 2013. Demographics and oncologic characteristics including tumor stage, pathology, BRCA status, and adjuvant treatment were reviewed, and reconstructive trends were assessed by racial group with a focus on reconstructive procedure, mastectomy volume, and implant characteristics. Statistical analysis was performed using SAS (version 9.2). One-hundred and sixty breast reconstructions were performed in 105 women; of which 50 per cent were African American, 26 per cent Hispanic, 22 per cent Caucasian, and 2 per cent Asian. Age, tumor stage, prevalence of triple negative disease, chemotherapy, and radiation treatment was comparable between groups. Rates of obesity, hypertension, and diabetes mellitus were slightly higher in African American and Hispanic cohorts, with more African American patients having one or more of these comorbidities as compared with the Caucasian and Hispanic cohorts (P = 0.047). Despite comparable positive BRCA testing rates, significant differences were seen in the percentage of bilateral mastectomy; 68 per cent African American, 48 per cent Caucasian, and 30 per cent Hispanic (P = 0.004). Hispanics predominantly underwent flap-based reconstruction (56%), while African American (74%) and Caucasian (60%) patients had a preference toward tissue expander reconstruction (P = 0.04 across all groups). African American and Hispanic presented with increased mastectomy weights and thus required higher implant volumes as compared with Caucasians that approached significance (P = 0.06 and P = 0.06). Implant size utilization followed a unimodal distribution for Caucasians, peaking at 500 cc; while African American and Hispanic demonstrated a bimodal distribution, peaking once at 550 cc and again at the max implant volume of 800 cc. This study of a large proportion of minority patients in an urban geographic setting offers an evolving understanding of breast reconstruction patterns. The data demonstrated unique findings of increased rates of bilateral implant-based reconstruction in African American women and unilateral flap-based reconstructions in Hispanic patients. Reconstructive decision-making seems to be greatly influenced by cultural and geographically driven preferences.