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.

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.

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.

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.

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.

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.

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].

Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus compared with matched controls.

BACKGROUND: Oxytocin, a hormone most commonly associated with parturition and lactation, may have additional roles in diabetes complications. We determined oxytocin levels in premenopausal women with type 1 diabetes mellitus (T1DM) compared with non-diabetic controls and examined associations of oxytocin with health behaviours, clinical factors, biomarkers, kidney function and bone health. Lower oxytocin was hypothesized for T1DM. METHODS: A cross-sectional study of premenopausal women with T1DM (n = 88) from the Wisconsin Diabetes Registry Study, a population-based cohort of incident T1DM cases, and matched non-diabetic controls (n = 74) was conducted. RESULTS: Women with T1DM had lower oxytocin levels than controls adjusting for caffeine and alcohol use (p = 0.03). Health behaviours associated with oxytocin differed between women with and without T1DM: oxytocin was negatively associated with hormonal contraceptive use (quantified as lifetime contraceptive oestrogen exposure) in women with T1DM (p = 0.003), whereas positively related to hormonal contraceptive use (quantified as never/former/current) in controls (p < 0.001). Oxytocin had a positive association with adiposity (waist-to-hip ratio and leptin) in women with T1DM and a negative relationship with adiposity (weight gain) in controls. In T1DM only, oxytocin was positively associated with caffeine intake (p = 0.01) and negatively associated with alcohol use (p = 0.01). Oxytocin was not related to glycemic control, kidney function or bone health in T1DM. CONCLUSIONS: Oxytocin levels are lower in women with T1DM than matched controls. Oxytocin also has opposing associations with hormonal contraceptives and adiposity in women with and without T1DM. Research is needed to determine if the altered oxytocin milieu in T1DM is associated with oxytocinher health outcomes.

Different health behaviours and clinical factors associated with bone mineral density and bone turnover in premenopausal women with and without type 1 diabetes.

BACKGROUND: Women with type 1 diabetes (T1DM) have an elevated fracture risk. We therefore compared the associations of health behaviours and clinical factors with bone mineral density (BMD) and bone remodelling between premenopausal women with and without T1DM to inform potential interventions. METHODS: Participants included women with T1DM (n = 89) from the Wisconsin Diabetes Registry Study and age-matched and race-matched controls without diabetes (n = 76). Peripheral (heel and forearm) and central (hip and spine) BMD, markers of bone resorption and formation, bone cell signalling, glycaemic control, and kidney function were assessed. Health behaviours and medical history were self-reported. RESULTS: In controls, but not in women with T1DM, older age was associated with lower bone resorption (p ≤ 0.006) and formation (p = 0.0007). Body mass index was positively associated with heel and forearm BMD in both controls and T1DM women (all p < 0.0001), but with hip and spine BMD only in controls (p ≤ 0.005). Worse glycaemic control during the previous 10 years, greater alcohol intake, history of smoking, and lack of physical activity were associated with poorer bone outcomes only in women with T1DM (all p ≤ 0.002), whereas use of hormonal contraceptives was related to low bone formation in both women with and without T1DM (all p ≤ 0.006). Diabetes duration, insulin dose, residual C-peptide, and kidney function were not associated with bone in T1DM. CONCLUSIONS: Age and body mass index may not predict bone health in T1DM women. However, modifiable behaviours such as optimizing glycaemic control, limiting substance and hormonal contraceptive use, and increasing physical activity may improve bone health in T1DM women.

The trajectory of IGF-1 across age and duration of type 1 diabetes.

BACKGROUND: Individuals with type 1 diabetes may have low IGF-1, related to insulinopenia and insulin resistance. There are few longitudinal studies of IGF-1 levels to establish its pattern in type 1 diabetes with duration and age, and to examine whether IGF-1 tracks within individuals over time. We examine age and duration trends, and the relationship of IGF-1 to gender, glycaemic control, insulin level and other factors. METHODS: Participants in the Wisconsin Diabetes Registry Study, an incident cohort study of type 1 diabetes diagnosed May 1987-April 1992, were followed for up to 18 years with IGF-1 samples up to age 45 for women and age 37 for men. RESULTS: IGF-1 is lower with type 1 diabetes than in normative samples. Although, the pattern across age resembles that in normative samples with a peak in adolescence and slow decline after age 20, the adolescent peak is delayed for women with type 1 diabetes. There was low to moderate tracking of IGF-1 within an individual. Higher insulin dose was associated with higher IGF-1 as was puberty, and female gender. Adjusted for these factors, IGF-1 declined rapidly across early diabetes duration. Lower HbA1c was most strongly related to higher IGF-1 at Tanner stages 1 and 2. CONCLUSIONS: IGF-1 is low in type 1 diabetes, with a delayed adolescent peak in women and is especially influenced by glycaemic control in early and pre-adolescence. High variability within an individual is likely a challenge in investigating associations between IGF-1 and long-term outcomes, and may explain contradictory findings.

Maternal body mass index (BMI) is independently associated with the control of diabetes mellitus in young patients.

OBJECTIVE: Investigate the cross-sectional association of glycemic control of ethnically diverse youth with diabetes mellitus with family characteristics. DESIGN: Family study of 91 youth (probands) with diabetes mellitus and 142 parents. RESULTS: Children's age and HbA1c averaged 11.9 years and 8.9%, respectively; 69% were minorities. After adjustment, poor glycemic control was associated with minority race/ethnicity, more television viewing, and higher maternal body mass index (BMI). Average HbA1c was 1.2 and 1.9% units higher for children of overweight and obese mothers, respectively (p = 0.004). CONCLUSIONS: The positive association between maternal body composition and child HbA1c likely represents the unique behavioral influence of mothers.

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.

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.

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.

Survival of human islets in microbeads containing high guluronic acid alginate crosslinked with Ca2+ and Ba2+.

BACKGROUND: The main hurdles to the widespread use of islet transplantation for the treatment of type 1 diabetes continue to be the insufficient number of appropriate donors and the need for immunosuppression. Microencapsulation has been proposed as a means to protect transplanted islets from the host's immune system. METHODS: This study investigated the function of human pancreatic islets encapsulated in Ca(2+) /Ba(2+) -alginate microbeads intraperitoneally transplanted in diabetic Balb/c mice. RESULTS: All mice transplanted with encapsulated human islets (n = 29), at a quantity of 3000 islet equivalent (IEQ), achieved normoglycemia 1 day after transplantation and retained normoglycemia for extended periods of time (mean graft survival 134 ± 17 days). In comparison, diabetic Balb/c mice transplanted with an equal amount of non-encapsulated human islets rejected the islets within 2 to 7 days after transplantation (n = 5). Microbeads retrieved after 232 days (n = 3) were found with little to no fibrotic overgrowth and contained viable insulin-positive islets. Immunofluorescent staining on the retrieved microbeads showed F4/80-positive macrophages and alpha smooth muscle actin-positive fibroblasts but no CD3-positive T lymphocytes. CONCLUSIONS: The Ca(2+) /Ba(2+) -alginate microbeads can protect human islets from xenogeneic rejection in immunocompetent mice without immunosuppression. However, grafts ultimately failed likely secondary to a macrophage-mediated foreign body reaction.

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).

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.

HLA-DQ haplotypes differ by ethnicity in patients with childhood-onset diabetes.

AIM: To understand the etiology of childhood-onset diabetes, we examined genetic risk markers, autoantibodies, and ß-cell function in a mixed race group of young patients. METHODS: One hundred and forty-five patients aged 0-17 at diagnosis (54% African American, 22% Caucasian, 16% Latino, 8% mixed-other) were studied at mean duration 6.9 ± 5.7 (range 0.1-28.5) yr, including human leukocyte antigen (HLA)-DQA1-DQB1 genotyping, stimulated C peptide (CP), glutamic acid decarboxylase, and insulinoma-associated antigen 2 antibodies (ABs). Based on no residual ß-cell function (CP-) and islet autoantibodies (AB+), 111 patients were classified with type 1 diabetes mellitus (T1DM), 22 were CP+ and AB- and thus considered to have type 2 diabetes mellitus (T2DM), and 12 patients had features of both T1DM and T2DM or mixed phenotype. RESULTS: Based on the presence of two high-risk HLA-DQA1/B1 haplotypes, 39% of African Americans, 81% of Caucasians, 70% of Latinos, and 67% of mixed-others were at high genetic risk. In patients with T1DM, 41% of African Americans, 80% of Caucasians, 73% of Latinos, and 63% of mixed-others were genetically susceptible. Thirty-one percent of African Americans, including 29% of those with T1DM, could not be characterized because their haplotypes had unknown T1DM associations. These unusual haplotypes comprised 11% in T1DM, 14% in T2DM, and 8% in patients with mixed phenotype. CONCLUSIONS: Fifty-nine percent of childhood-onset patients with T1DM were identified with high genetic risk based on known HLA-DQA1/B1 associations. Many non-Caucasian patients carry HLA-DQ alleles whose association with T1DM is undetermined. Genetic approaches can provide insights into the etiology and appropriate treatment of childhood-onset diabetes but only if sufficient data are available in diverse ethnic groups.

Onset features and subsequent clinical evolution of childhood diabetes over several years.

AIM: To explore whether it is possible to predict a child's eventual diabetes phenotype using characteristics at initial presentation, we reassessed 111 young patients on average 7.8 ± 4.2 (2.2-19.7) [mean ± SD (range)] years after diagnosis. METHODS: Medical records at diagnosis for 111 patients, aged 0-17, were compared with their follow-up characteristics including stimulated C-peptide (CP) and islet autoantibodies (AB). RESULTS: Initially, 18 patients were obese; 9 displayed other type 2 diabetes (T2DM) features (polycystic ovary syndrome, acanthosis, diagnosed T2DM); the remaining 84 had a classic type 1 diabetes (T1DM) presentation. At follow-up, 83 patients (75%) with no measured CP were classified as T1DM; 17 (15%) were CP+ and AB- and thus considered T2DM. Eleven patients with both T1DM and T2DM features were classified as having mixed diabetes phenotype (MDM). One-fifth (22 subjects) changed presumed phenotype at follow-up. In multivariable models, T1DM patients were younger at diagnosis, had higher initial glucose values, were more likely to have experienced ketoacidosis, and less likely to be obese or of African American ethnicity. CONCLUSIONS/INTERPRETATION: Ten percent of subjects had MDM and 15% had T2DM at ∼8 years' duration. Although no onset feature was completely reliable, ketoacidosis and hyperglycemia were more likely to predict T1DM; obesity and African American ethnicity made T2DM more likely. At diagnosis, features of T2DM in addition to obesity were strongly predictive of eventual T2DM phenotype. Given the significant percentage who changed or had mixed phenotype, careful tracking of all young people with diabetes is essential to correctly determine eventual disease type.

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.