The impact of a preoperative evaluation process on weight reduction and glycemic control in patients undergoing bariatric and metabolic surgery.

Introduction: Metabolic surgery is a sustainable intervention for obesity and type 2 diabetes. Preoperative education optimizes weight loss and glycemic control outcomes. Objective: This study aimed to determine the effect of a generalized preoperative evaluation process (PEP) in patients who underwent bariatric surgery on weight loss and glycemic control pre- and post-surgery. Methods: Data were retrospectively collected and analyzed for patients with type 2 diabetes who underwent bariatric surgery between 2010 and 2016. Patients were categorized into two groups determined by participation in the PEP. The groups were named the PEP group and non-PEP group. The correlation among engagement in the PEP was determined using the chi-square test and t-test. Statistical analysis with p < 0.05 was deemed significant. Results: 129 patients were included in the study; 86 females (67%) and 43 males (33%). Fifty-nine patients (46%) engaged in the PEP and 70 (54%) patients did not engage in the PEP. A greater reduction in weight loss was observed in the PEP group versus the non-PEP group from initial enrollment to pre-surgery (14.3 ± 9.2 kg vs. 11.6 ± 9.2 kg; p = 0.11), and from pre-surgery to 2-years post-surgery (20.6 ± 14.8 kg vs. 16.9 ± 15.6 kg; p = 0.17). A greater reduction in HbA1c from initial enrollment to pre-surgery was seen in the PEP group versus the non-PEP group (0.90 ± 1.28% vs. 0.63 ± 1.07%); however, this was not maintained from pre-surgery to 2-year post-surgery (0.51 ± 1.18% vs. 0.70 ± 1.73%). In both cases, the statistical difference was insignificant. Conclusion: The PEP was not associated with improvements in short-term weight loss or glycemic control pre-surgery and a 2-years post-surgery. Patients may benefit from individually tailored preoperative weight management strategies.

How effective is public health policy in Scotland on vitamin D deficiency during pregnancy?

OBJECTIVE: To evaluate the uptake of universal vitamin D supplementation during pregnancy, its effectiveness in preventing vitamin D deficiency and the factors associated with these. DESIGN: The regional public health organisation in Ayrshire, Scotland has a policy of universal provision of vitamin D supplements (10 µg/d) to all pregnant women for the duration of their pregnancy. Pregnant women in this area were recruited at their 12-week antenatal appointment. Blood samples were collected at the 12-week and 34-week appointments. To account for the seasonal variation, women were recruited in two cohorts: summer and winter. Telephone interviews were conducted at 34 weeks to assess the uptake of vitamin D supplements during pregnancy. Other variables were obtained from medical records. SETTING: The study was conducted in the NHS Ayrshire and Arran Health Board in Scotland. PARTICIPANTS: 612 pregnant women (aged 15-44 years) living in Ayrshire (latitude 55°), Scotland. RESULTS: Sixty-six percentage took supplementation as recommended. Consumption of supplementation was significantly associated with a higher median serum 25-hydroxyvitamin D concentrations at 34 weeks. Despite this at 34 weeks, 33 % of the summer cohort had insufficient or deficient vitamin D status, while 15 % of the winter cohort had insufficient or deficient status. In multivariable analysis, only adherence and season were independent predictors of vitamin D status. CONCLUSIONS: While supplementation improved and maintained vitamin D status during pregnancy, it was not adequate to ensure all those insufficient at 12 weeks achieved sufficient status at the end of pregnancy.

Tear Fluid Biomarkers and Quality of Life in People with Type 2 Diabetes and Dry Eye Disease.

Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED, were assessed. Patients were classified into four groups: T2D + DED (n = 47), T2D-only (n = 41), DED-only (n = 17) and healthy controls (n = 17). All patients underwent the Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality of Life (DEQS) questionnaires, tear evaporation rate (TER), fluorescein tear break-up time (fTBUT), corneal fluorescein staining (CFS) and Schirmer 1 test assessments. Six metabolic proteins and 14 inflammatory cytokines were analyzed with multiplex bead analysis. Interleukin (IL)-6 and IL-8 concentrations in tears were significantly higher in the T2D + DED group, and these biomarkers were positively correlated with CFS. In addition, tear IL-6 was negatively correlated with fTBUT in the T2D + DED group. Clinical signs of DED in the T2D + DED group were similar to the DED-only group. The T2D + DED group had more patients with moderate and severe DED (versus the DED-only group), suggesting a different pathogenesis for DED in T2D versus DED-only. Therefore, IL-6 and IL-8 could potentially be diagnostic biomarkers of DED in T2D.

Liver fibrosis markers and all cause mortality in people with type 2 diabetes: A population based study (The Ayrshire Diabetes Outcomes Cohort (ADOC) Study).

AIMS: To describe the distribution of the biomarker scores Fibrosis-4 (FIB4), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index (APRI), and the associations between risk categories and all-cause mortality. MATERIALS AND METHODS: This was a retrospective cohort study of 12 589 patients, with follow-up from January 2012 until November 2021. The cut-off points used to identify low risk were: FIB4 <1.3 if aged <65 years or <2.0 if aged ≥65 years; NFS < -1.455 if aged <65 years or <0.12 if aged ≥ 65 years; APRI <1 (independent of age). High-risk cut-off points were FIB4 >2.67, NFS >0.676 and APRI ≥1 (all independent of age). Multivariable Cox regression analysis was performed to assess the association between liver fibrosis scores and all-cause mortality. RESULTS: The mean ± standard deviation age was 65.2 ± 12.1 years, 54.5% were men and the median (interquartile range) diabetes duration was 5.8 (2.8-9.3) years. The prevalence of high-risk categories was 6.1% for FIB4, 23.5% for NFS and 1.6% for APRI. During a median follow-up of 9.8 years, 3925 patients (31.1%) died, resulting in a crude mortality rate of 40.4 per 1000 person-years. The overall adjusted all-cause mortality hazard ratios (95% confidence intervals [CIs]) in the high- compared with low-fibrosis-risk groups were 3.69 (1.95-2.75) for FIB4, 2.32 (2.88-4.70) for NFS, and 3.92 (2.88-5.34) for APRI. Stratified adjusted all-cause mortality hazard ratios for individuals under 65 years and people over 65 years of age at cohort entry were 3.89 (95% CI 2.99-5.05) and 1.44 (95% CI 1.28-1.61) for FIB4, 2.50 (95% CI 1.89-3.18) and 1.35 (95% CI 1.24-1.48) for NFS and 3.74 (95% CI 2.73-5.14) and 1.64 (95% CI 1.24-2.17) for APRI. CONCLUSIONS: All three fibrosis risk scores were positively associated with all-cause mortality in people with type 2 diabetes, with higher relative risks in younger than older people. Effective interventions are required to minimize excess mortality in people at high risk of liver fibrosis.

Hypergonadotropic hypogonadism and chromosomal aberrations: clinical heterogeneity and implications on the health of elderly men, case series.

BACKGROUND: Hypogonadism in older men is often considered as late onset hypogonadism. However, this clinical condition results from primary testicular failure which could be of genetic origin with Klinefelter syndrome being the most common chromosomal abnormality associated with it. CASE PRESENTATION: We report a heterogeneous group of cases who were diagnosed with hypergonadotropic hypogonadism in their adulthood and were found to have rare chromosomal aberrations. All were elderly men (in their 70 s and 80 s) for whom the diagnosis was made during the evaluation of incidental symptoms suggestive of endocrinopathy. The first had hyponatremia; the other two had gynaecomastia and features of hypogonadism noted during admission for various acute medical problems. With respect to their genetic results; the first had a male karyotype with balanced reciprocal translocation between the long arm of chromosome 4 and the short arm of chromosome 7. The second case had a male karotype with one normal X chromosome and an isochrome for the short arm of the Y chromosome. The third case was an XX male with unbalanced translocation between the X & Y chromosomes with retention of the SRY locus. CONCLUSION: Hypergonadotrophic hypogonadism in the elderly, may be due to chromosomal aberrations, resulting in heterogeneous and diverse clinical phenotypes. Vigilance must be exercised when seeing cases with subtle clinical findings. This report suggests that in selected cases of adult hypergonadotropic hypogonadism, chromosomal analysis may be indicated.

Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.

OBJECTIVE: To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study. RESEARCH DESIGN AND METHODS: A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial. RESULTS: Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17). CONCLUSIONS: Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.

Epidemiology, management and outcome of candidaemia in patients with diabetes.

BACKGROUND: Candidaemia is the commonest fungal bloodstream infection in hospitalised patients. Diabetes is one of the risk factors for mortality from candidaemia. METHODS: We compared the epidemiology, clinical characteristics and management of candidaemia in patients with and without diabetes. RESULTS: Over a 10-year period, 200 episodes of Candida bloodstream infection were documented. Patients with diabetes were younger (58.7 vs 65.5 years), less likely to be suffering from cancer (21.8% vs 36%), and had significantly lower 30-day and 90-day crude mortality (17.2% vs 35.6% and 28.4% vs 48.6%, respectively). Candida glabrata was more common in patients with diabetes (39.3% vs 29.7%). Based on European Confederation of Medical Mycology (ECMM) quality indicators, the management of patients with and without diabetes was similar. DISCUSSION: Our study highlights the importance of epidemiological data in relation to candidaemia in patients with diabetes and the growing threat of invasive C. glabrata infection in this subset of patients.

Predisposing factors for the development of diabetic ketoacidosis with lower than anticipated glucose levels in type 2 diabetes patients on SGLT2-inhibitors: a review.

PURPOSE: SGLT2-inhibitors (SGLT-2i) have been linked to the risk of potential life-threatening diabetic ketoacidosis (DKA). The U.S. Food and Drug Administration and the European Medicines Agency issued warnings in 2015 and 2016 respectively on the predisposing factors to the development of DKA in individuals on an SGLT2i. New predisposing factors to DKA are still being discovered with the use of SGLT-2i. The list by FDA and EMA is yet to be updated. This article aims to provide a holistic list that includes the newer factors that have been implicated in the development of DKA. The overall aim is to guide physicians in prescribing this class of drugs for type 2 diabetes mellitus (T2D). METHOD: A search was done using PUBMED, Google Scholar, and Directory of Open Access Journals with the following words: SGLT-2 Inhibitors AND Ketoacidosis were entered. We included articles from 2000 to 2020, those in English, those involving any of the approved SGLT2i medications in T2D patients, and studies that focused on DKA linked to SGLT-2i. These articles were reviewed, and relevant data extracted and compiled. RESULTS AND CONCLUSION: The review has revealed that predisposing factors include (excess) alcohol consumption, female gender, starvation due to illness or fasting, withholding the use of SGLT2i for less than 48 h peri-operatively, and the existence of a variations in the expression of SGLT2 receptors. Patients should be advised on "sick day rules," and if a patient becomes unwell while on an SGLT2i, they should be advised to withhold the medication for the duration of the intercurrent illness.

Quantitative levels of serum N-glycans in type 1 diabetes and their association with kidney disease.

We investigated associations of quantitative levels of N-glycans with hemoglobin A1c (HbA1c), renal function and renal function decline in type 1 diabetes. We measured 46 total N-glycan peaks (GPs) on 1565 serum samples from the Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO) and a pool of healthy donors. Quantitation of absolute abundance of each GP used 2AB-labeled mannose-3 as a standard. We studied cross-sectional associations of GPs and derived measures with HbA1c, albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR), and prospective associations with incident albuminuria and final eGFR. All GPs were 1.4 to 3.2 times more abundant in SDRTN1BIO than in the healthy samples. Absolute levels of all GPs were slightly higher with higher HbA1c, with strongest associations for triantennary trigalactosylated disialylated, triantennary trigalactosylated trisialylated structures with core or outer arm fucose, and tetraantennary tetragalactosylated trisialylated glycans. Most GPs showed increased abundance with worsening ACR. Lower eGFR was associated with higher absolute GP levels, most significantly with biantennary digalactosylated disialylated glycans with and without bisect, triantennary trigalactosylated trisialylated glycans with and without outer arm fucose, and core fucosylated biantennary monogalactosylated monosialylated glycans. Although several GPs were inversely associated prospectively with final eGFR, cross-validated multivariable models did not improve prediction beyond clinical covariates. Elevated HbA1c is associated with an altered N-glycan profile in type 1 diabetes. Although we could not establish GPs to be prognostic of future renal function decline independently of HbA1c, further studies to evaluate their impact in the pathogenesis of diabetic kidney disease are warranted.

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.

BACKGROUND: We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. METHODS: In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. FINDINGS: Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304-1·494; p<0·0001, compared with the risk in those without diabetes. The OR was 2·396 (1·815-3·163; p<0·0001) in type 1 diabetes and 1·369 (1·276-1·468; p<0·0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more anti-diabetic and other medication (all p<0·0001), and have been a smoker (p=0·0011). The cross-validated predictive model of fatal or critical care unit-treated COVID-19 in people with diabetes had a C-statistic of 0·85 (0·83-0·86). INTERPRETATION: Overall risks of fatal or critical care unit-treated COVID-19 were substantially elevated in those with type 1 and type 2 diabetes compared with the background population. The risk of fatal or critical care unit-treated COVID-19, and therefore the need for special protective measures, varies widely among those with diabetes but can be predicted reasonably well using previous clinical history. FUNDING: None.

Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications.

OBJECTIVE: To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. <5 pmol/L were as follows: insulin dose at baseline, 27% lower (P = 2 × 10-39); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10-13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to <200 pmol/L with <5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10-8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.

Diurnal patterns of objectively measured sedentary time and interruptions to sedentary time are associated with glycaemic indices in type 2 diabetes.

OBJECTIVES: To investigate diurnal patterns of sedentary time and interruptions to sedentary time and their associations with achievement of pre-meal glucose, post-meal glucose, bedtime glucose and the dawn phenomenon targets and with duration of hypoglycaemia, euglycaemia, hyperglycaemia and above target range. DESIGN: Intensive longitudinal study. METHODS: In 37 adults with type 2 diabetes, the FreeStyle Libre and activPAL3 were used to monitor glucose and sedentary time and interruptions to sedentary time in the morning (07:00-12:00), afternoon (12:00-17:00) and evening (17:00-23:00) for 14 days. Diurnal patterns of sedentary behaviour and associations with glycaemic indices were assessed using repeated measures ANOVA and linear regressions. RESULTS: Sedentary time was significantly higher in the evening (43.47±7.37min/h) than the morning (33.34±8.44min/h) and afternoon (37.26±8.28min/h). Interruptions to sedentary time were significantly lower in the evening (2.64±0.74n/h) than the morning (3.69±1.08n/h) and afternoon (3.06±0.87n/h). Sedentary time in the morning and afternoon was associated with lower achievement of the dawn phenomenon target. Sedentary time in the evening was associated with lower achievement of post-lunch glucose target. Interruptions to sedentary time in the morning and afternoon were associated with higher achievement of pre-dinner glucose target. Interruptions to sedentary time in the evening showed beneficial associations with achievement of post-dinner glucose and bedtime glucose targets and euglycaemia. CONCLUSIONS: Prolonged sedentary behaviour is high in the evening. Interruptions to sedentary time, particularly in the evening, have beneficial associations with glycaemic indices. Interventions targeting interruptions to sedentary time in the evening may be more clinically relevant.

Predictors of poor adherence to antidiabetic therapy in patients with type 2 diabetes: a cross-sectional study insight from Ethiopia.

BACKGROUND: Poor adherence to the medical regimen is a major clinical problem in the management of patients with diabetes. This study sought to investigate the level of medication adherence to antidiabetic therapy and to identify possible predictors of poor adherence. METHODS: A hospital based cross-sectional study was conducted from July 2018 to June 2019 among randomly selected follow-up T2D patients at a hospital diabetes clinic. Data were collected through patient interviews, followed by medical chart review. Adherence to antidiabetic therapy that we assessed patients' responses using validated Brief Medication Questionnaire (BMQ). To identify predictors of poor medication adherence, binary logistic regression analyses were performed using SPSS version 25. Statistical significance was set at p value ≤ 0.05. RESULTS: Of the total 357 study participants, 25% were non-adherent to their antidiabetic therapy. Predictors statistically associated with poor adherence were; being female gender (AOR = 1.71, 95% CI 1.01-2.76), and presence of at least one diabetic complication (AOR = 2.02, 95% CI 1.02-3.22). Participants with having at least primary level of education were more likely to adhere to anti-diabetes medication (AOR = 0.42, 95% CI 0.18-0.96). The most common self-reported reasons for non-adherence were forgetfulness, unavailability of medication plus the unaffordability of anti-diabetes medications. CONCLUSIONS: The proportion of participants' adherent to anti-diabetes therapies was suboptimal. Being female, the presence of chronic diabetic complications and having no formal education were the main predictors of poor adherence. Strategies that aimed at improving adherence to antidiabetic medications deemed to be compulsory.

Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland.

OBJECTIVE: To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications. RESEARCH DESIGN AND METHODS: We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications. RESULTS: The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21-1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37-2.03]), and worse renal function (1.96 [1.03-3.74] for estimated glomerular filtration rate levels <30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66-0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78-2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications. CONCLUSIONS: Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.

Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes.

AIMS/HYPOTHESIS: We examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR). METHODS: From the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min-1 [1.73 m]-2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others' prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min-1 [1.73] m-2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data. RESULTS: Seven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min-1 [1.73 m]-2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10-3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min-1 [1.73 m]-2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min-1 [1.73 m]-2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR. CONCLUSIONS/INTERPRETATION: A parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Cancer has overtaken cardiovascular disease as the commonest cause of death in Scottish type 2 diabetes patients: A population-based study (The Ayrshire Diabetes Follow-up Cohort study).

AIMS/INTRODUCTION: The increased mortality risk associated with diabetes is well established. The aim of the present study was to determine the causes of death of people with type 2 diabetes in Ayrshire and Arran, Scotland, between 2009 and 2014, and compare them with the national mortality rates. MATERIALS AND METHODS: The primary causes of death were collated. The causes of death were clustered into nine categories: heart disease, stroke, infection, renal failure, respiratory disorders, cancer, mental health, decompensated diabetes and other. The total rates were compared with national rates using the standardized mortality ratio (SMR), and then individually with heart disease, cerebrovascular disease and cancer. RESULTS: There were 2116 deaths with the SMR, and 145 of those were caused by type 2 diabetes (n = 16,643; 95% confidence interval 139-152; P < 0.01). The SMR was >100 in all age bands, particularly in the younger age bands (P < 0.01). The SMR was consistently higher for women (P < 0.01). The SMR for heart disease was significantly >100 for both sexes in all age bands <65 years (P < 0.05). There was no difference in mortality causes related to the duration of diabetes. The most common cause of death was cancer (27.8%), followed by heart disease (24.1%). The SMR for cancer deaths was significantly elevated in women (120, 95% CI 104-137; P < 0.05). CONCLUSIONS: This study confirmed increased mortality risk in type 2 diabetes patients, and suggests that where cardiovascular risk factors are being treated aggressively, cancer takes on a greater importance in the cause of death. Should greater consideration now be given for cancer as a complication of diabetes?

Impact of free-living pattern of sedentary behaviour on intra-day glucose regulation in type 2 diabetes.

PURPOSE: To investigate how the pattern of sedentary behaviour affects intra-day glucose regulation in type 2 diabetes. METHODS: This intensive longitudinal study was conducted in 37 participants with type 2 diabetes (age, 62.8 ± 10.5 years). Glucose and sedentary behaviour/physical activity were assessed with a continuous glucose monitoring (Abbott FreeStyle Libre) and an activity monitor (activPAL3) for 14 days. Multiple regression models with generalised estimating equations (GEEs) approach were used to assess the associations of sedentary time and breaks in sedentary time with pre-breakfast glucose, pre-lunch glucose, pre-dinner glucose, post-breakfast glucose, post-lunch glucose, post-dinner glucose, bedtime glucose, the dawn phenomenon, time in target glucose range (TIR, glucose 3.9-10 mmol/L) and time above target glucose range (TAR, glucose > 10 mmol/L). RESULTS: Sedentary time was associated with higher pre-breakfast glucose (p = 0.001), pre-dinner glucose (p < 0.001), post-lunch glucose (p = 0.005), post-dinner glucose (p = 0.013) and the dawn phenomenon (p < 0.001). Breaks in sedentary time were associated with lower pre-breakfast glucose (p = 0.023), pre-dinner glucose (p = 0.023), post-breakfast glucose (p < 0.001) and the dawn phenomenon (p = 0.004). The association between sedentary time and less TIR (p = 0.022) and the association between breaks in sedentary time and more TIR (p = 0.001) were also observed. CONCLUSIONS: Reducing sedentary time and promoting breaks in sedentary time could be clinically relevant to improve intra-day glucose regulation in type 2 diabetes.