Parallel assessment of albuminuria and plasma sTNFR1 in people with type 2 diabetes and advanced chronic kidney disease provides accurate prognostication of the risks of renal decline and death.

Identification of people with diabetes and chronic kidney disease at high-risk of early mortality is a priority to guide intensification of therapy. We aimed to investigate the complementary prognostic value of baseline urine albumin-to-creatinine ratio (uACR) and plasma soluble tumour necrosis factor receptor-1 (sTNFR1) with respect to early mortality and renal functional decline in a population with type 2 diabetes and advanced chronic kidney disease. We measured plasma sTNFR1 in people with type 2 diabetes (HbA1c ≥ 48 mmol/mol) at 2 hospital sites in Dublin between October 15th, 2014 and July 17th, 2015. In a subgroup of patients with advanced chronic kidney disease at baseline (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/BSA) (n = 118), we collected clinical and longitudinal laboratory data to investigate relationships between sTNFR1 and renal and mortality endpoints by multivariable linear mixed-effects models and Cox proportional hazards regression models. The cohort was 64% male and 97% Caucasian. Mean age was 74 years, with a median type 2 diabetes duration of 16 years. Mean CKD-EPI eGFR was 42 mL/min/BSA and median [IQR] uACR was 3 [11] mg/mmol. Twenty-three (39%) people in quartiles 3 and 4 for plasma sTNFR1 died over 4-year follow-up. After adjustment for clinical variables, annual CKD-EPI eGFR decreased by - 0.56 mL/min/BSA/year for each logarithm unit increase in baseline uACR, corresponding to an annual loss of renal function of 3% per year. Furthermore, elevated uACR, but not sTNFR1, increased the risk of ≥ 40% decline in CKD-EPI eGFR (HR 1.5, p = 0.001) and doubling of serum creatinine (HR 2.0, p < 0.001). Plasma sTNFR1 did not predict a more negative trajectory in eGFR slope. However, for those people in quartiles 3 and 4 for plasma sTNFR1, an increased risk of incident mortality was detected (HR 4.9, p = 0.02). No such association was detected for uACR. In this elderly cohort of patients with type 2 diabetes and chronic kidney disease, sTNFR1 predicted short-to-medium term mortality risk but not risk of progressive renal functional decline. In contrast, parallel assessment of uACR predicted renal functional decline but not mortality, highlighting the complementary prognostic information provided by both parameters.

Validating the association between plasma tumour necrosis factor receptor 1 levels and the presence of renal injury and functional decline in patients with Type 2 diabetes.

AIMS: Elevated plasma soluble tumour necrosis factor receptor 1 (TNFR1) predicts long-term progression of chronic kidney disease. We investigated the association between elevated TNFR1 and the presence of renal disease in patients with Type 2 diabetes mellitus registering a haemoglobin A1c (HbA1c) >48mmol/mol despite medical therapy. METHODS: Using sensitivity, specificity and regression analyses we interrogated the association between plasma TNFR1 and presence of chronic kidney disease as assessed by the presence of microalbuminuria and/or an estimated glomerular filtration rate of less than 60ml/min/1.73m2 (stages 3-5 chronic kidney disease). The association of TNFR1 with C-reactive protein and leptin-adiponectin ratio as plasma markers of systemic inflammation and adipose stress respectively was also investigated. RESULTS: Upper quartile TNFR1 is independently associated with elevated urinary albumin-creatinine ratios, reductions in eGFR and strongly predicts the presence of stages 3-5 chronic kidney disease in regression modelling. Elevated TNFR1 levels are associated with increased plasma C-reactive protein and augmented leptin-adiponectin ratio. CONCLUSIONS: Our study confirms plasma TNFR1 as a surrogate of renal structural and functional impairment in patients with type 2 diabetes mellitus. Association of TNFR1 with markers of systemic inflammation and adipose stress indicates that TNFR1 may be a biomarker of these processes as components of the pathogenesis of diabetic kidney disease.

Risk Factors for Macro- and Microvascular Complications among Older Adults with Diagnosed Type 2 Diabetes: Findings from The Irish Longitudinal Study on Ageing.

Objective. To explore risk factors for macro- and microvascular complications in a nationally representative sample of adults aged 50 years and over with type 2 diabetes in Ireland. Methods. Data from the first wave of The Irish Longitudinal Study on Ageing (TILDA) (2009-2011) was used in cross-sectional analysis. The presence of doctor diagnosis of diabetes, risk factors, and macro- and microvascular complications were determined by self-report. Gender-specific differences in risk factor prevalence were assessed with the chi-squared test. Binomial regression analysis was conducted to explore independent associations between established risk factors and diabetes-related complications. Results. Among 8175 respondents, 655 were classified as having type 2 diabetes. Older age, being male, a history of smoking, a lower level of physical activity, and a diagnosis of high cholesterol were independent predictors of macrovascular complications. Diabetes diagnosis of 10 or more years, a history of smoking, and a diagnosis of hypertension were associated with an increased risk of microvascular complications. Older age, third-level education, and a high level of physical activity were protective factors (p < 0.05). Conclusions. Early intervention to target modifiable risk factors is urgently needed to reduce diabetes-related morbidity in the older population in Ireland.

Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis.

BACKGROUND: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. METHODS: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random-effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. RESULTS: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend ≤ 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5-25.2 % retinopathy; 3.2-32.0 % neuropathy; 2.5-5.2 % nephropathy). CONCLUSIONS: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland.

Trends in the incidence of lower extremity amputations in people with and without diabetes over a five-year period in the Republic of Ireland.

AIMS: To describe trends in the incidence of non-traumatic amputations among people with and without diabetes and estimate the relative risk of an individual with diabetes undergoing a lower extremity amputation compared to an individual without diabetes in the Republic of Ireland. METHODS: All adults who underwent a nontraumatic amputation during 2005 to 2009 were identified using HIPE (Hospital In-patient Enquiry) data. Participants were classified as having diabetes or not having diabetes. Incidence rates were calculated using the number of discharges for diabetes and non-diabetes related lower extremity amputations as the numerator and estimates of the resident population with and without diabetes as the denominator. Age-adjusted incidence rates were used for trend analysis. RESULTS: Total diabetes-related amputation rates increased non-significantly during the study period; 144.2 in 2005 to 175.7 in 2009 per 100,000 people with diabetes (p = 0.11). Total non-diabetes related amputation rates dropped non-significantly from 12.0 in 2005 to 9.2 in 2009 per 100,000 people without diabetes (p = 0.16). An individual with diabetes was 22.3 (95% CI 19.1-26.1) times more likely to undergo a nontraumatic amputation than an individual without diabetes in 2005 and this did not change significantly by 2009. DISCUSSION: This study provides the first national estimate of lower extremity amputation rates in the Republic of Ireland. Diabetes-related amputation rates have remained steady despite an increase in people with diabetes. These estimates provide a base-line and will allow follow-up over time.

Diabetes- and nondiabetes-related lower extremity amputation incidence before and after the introduction of better organized diabetes foot care: continuous longitudinal monitoring using a standard method.

OBJECTIVE: There is a lack of continuous longitudinal population-based data on lower extremity amputation (LEA) in the U.K. We present here accurate data on trends in diabetes-related (DR) LEAs and non-DRLEAs in the South Tees area over a continuous 5-year period. RESEARCH DESIGN AND METHODS: All cases of LEA from 1 July 1995 to 30 June 2000 within the area were identified. Estimated ascertainment using capture-recapture analysis approached 100% for LEAs in the area. Data were collected longitudinally using the standard method of the Global Lower Extremity Amputation Study protocol. RESULTS: Over 5 years there were 454 LEAs (66.3% men) in the South Tees area, of which 223 were diabetes related (49.1%). Among individuals with diabetes, LEA rates went from 564.3 in the first year to 176.0 of 100,000 persons with diabetes in the fifth year. Over the same period, non-DRLEAs increased from 12.3 to 22.8 of 100,000 persons without diabetes. The relative risk of a person with diabetes undergoing an LEA went from being 46 times that of a person without diabetes to 7.7 at the end of the 5 years. The biggest improvement in LEA incidence was seen in the reduction of repeat major DRLEAs. CONCLUSIONS: Our data show that in the South Tees area at a time when major non-DRLEA rates increased, major DRLEA rates have fallen. These diverging trends mark a significant improvement in care for patients with diabetic foot disease as a result of better organized diabetes care.