Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study

Objective To examine short and long term time trends in mortality among patients with early onset (age 0-14 years) and late onset (15-29 years) type 1 diabetes and causes of deaths over time

Perceived Stress and Adherence to the Dietary Recommendations and Blood Glucose Levels in Type 1 Diabetes

Stress may negatively impact self-management of diabetes and thereby deteriorate glycaemic control. Eating is the most frequently reported stress-release method. In this study, we investigated the association between perceived stress (PS), dietary adherence, and glycaemic control. Data from participants in the FinnDiane Study with type 1 diabetes who had completed a diet questionnaire and Cohen's perceived stress scale (PSS) were included. In addition to using a continuous PSS score, participants were divided into three groups based on the PSS scores: the first PSS quartile, low levels of PS; second and third quartiles, moderate levels of PS; and fourth quartile, high levels of PS. A diet score reflecting the level of adherence to dietary recommendations was calculated. Analyses were conducted in the whole sample and in subgroups divided by body mass index (BMI = 25 kg/m(2)). In the whole sample, high PS and continuous stress score were negatively associated with the diet score and with adherence to fish, fresh vegetable, low-fat liquid milk product, and vegetable oil-based cooking fat recommendations. The stress score was negatively associated with the diet score both in lean and in those overweight or obese. However, fish and fresh vegetable recommendations were only affected in those with corpulence. PS was not associated with mean blood glucose concentrations in the whole sample. When divided by BMI status, worse glycaemic control was observed in lean subjects reporting stress. In individuals with overweight or obesity, instead, high glucose concentrations were observed regardless of the level of perceived stress. Interventions to improve stress management could improve dietary adherence and glycaemic control and could thereby have the potential to improve long-term health and well-being of individuals with type 1 diabetes.Peer reviewe

Waist-Height Ratio and the Risk of Severe Diabetic Eye Disease in Type 1 Diabetes : A 15-Year Cohort Study

Context: Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown. Objective: To investigate the associations between body composition and SDED in adults with T1D. Methods: From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic. Results: During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z= 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z= 2.22).The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR >= 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages. Conclusions: WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.Peer reviewe

Arterial Stiffness Predicts Mortality in Individuals With Type 1 Diabetes

OBJECTIVE Type 1 diabetes is accompanied by a significant burden of cardiovascular disease (CVD), which is poorly explained by traditional risk factors. We therefore aimed to explore whether arterial stiffness estimated by the augmentation index (AIx) predicts mortality in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS After baseline examination comprising pulse wave analysis by applanation tonometry alongside assessment of traditional cardiovascular risk factors, 906 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study were followed up for a median of 8.2 years (interquartile range 5.7-9.7). Associations between baseline hemodynamics, including AIx, and all-cause mortality as well as a composite of cardiovascular and/or diabetes-related mortality were investigated using multivariable Cox regression models. RESULTS The 67 individuals who died during follow-up had higher baseline AIx (median 28% [interquartile range 21-33] vs. 19% [9-27];P<0.001) compared with those alive. This association was independent of conventional risk factors (age, sex, BMI, HbA(1c), estimated glomerular filtration rate [eGFR], and previous CVD event) in Cox regression analysis (standardized hazard ratio 1.71 [95% CI 1.10-2.65];P= 0.017) and sustained in a subanalysis of individuals with chronic kidney disease. Similarly, higher AIx was associated with the composite secondary end point of cardiovascular and diabetes-related death (N= 53) after adjustments for sex, BMI, eGFR, previous CVD event, and height (standardized hazard ratio 2.30 [1.38-3.83];P= 0.001). CONCLUSIONS AIx predicts all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in individuals with type 1 diabetes, independent of established cardiovascular risk factors.Peer reviewe

Meal timing, meal frequency, and breakfast skipping in adult individuals with type 1 diabetes - associations with glycaemic control

We assessed meal timing, meal frequency, and breakfast consumption habits of adult individuals with type 1 diabetes (n = 1007) taking part in the Finnish Diabetic Nephropathy Study, and studied whether they are associated with glycaemic control. Data on dietary intake and blood glucose measurements were retrieved from food records. HbA(1c) was measured at the study visit. In the whole sample, four peaks of energy intake emerged. Energy intake was the greatest in the evening, followed by midday. Altogether 7% of the participants reported no energy intake between 05:00 and 09:59 (breakfast skippers). While breakfast skippers reported lower number of meals, no difference was observed in the total energy intake between those eating and omitting breakfast. In a multivariable model, skipping breakfast was associated with higher mean blood glucose concentrations and lower odds of good glycaemic control. A median of 6 daily meals was reported. Adjusted for confounders, the number of meals was negatively associated with HbA(1c), and the mean of the blood glucose measurements, but positively associated with the variability of these measurements. Our observations support the habit of a regular meal pattern, including consumption of breakfast and multiple smaller meals for good glycaemic control in adults with type 1 diabetes. However, an increase in the blood glucose variability may additionally be expected with an increase in the number of meals eaten.Peer reviewe

The Self-reported Use of Probiotics is Associated with Better Glycaemic Control and Lower Odds of Metabolic Syndrome and its Components in Type 1 Diabetes

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Long-term Mortality After Kidney Transplantation in a Nationwide Cohort of Patients With Type 1 Diabetes in Finland

OBJECTIVE To examine time trends inmortality rates and causes of death in patients with type 1 diabetes and end-stage renal disease on dialysis and after kidney transplantation. RESEARCH DESIGN AND METHODS In a nationwide retrospective cohort analysis, all patients with type 1 diabetes in Finland who received a kidney transplant alone were compared with patients who remained on dialysis. The main outcome was patient survival after starting dialysis. The cohort was divided into dialysis, functioning kidney transplant, and dialysis after transplant loss. Causes of death were retrieved and standardized mortality ratios calculated. RESULTS We studied 2,383 patients. Patients survived a median of 15.9 years after a successful transplant, 11.2 years if transplant function was lost, and 2.9 years if they remained on chronic dialysis. Standardized mortality ratio decreased in all subgroups during the past four decades: from 2005 onwards, it was 3.9 in patients receiving a kidney transplant, 11.5 in patients with graft loss, and 32.5 in patients on dialysis. The most common cause of death in all patients was ischemic heart disease (45%) followed by infection (18%), which was more common in patients on dialysis. CONCLUSIONS Kidney transplantation is the treatment of choice for patients with type 1 diabetes and end-stage renal disease because it substantially reduces the excess death risk when compared with dialysis. Even when kidney graft function is lost, the excess death risk is still considerably lower. Although overall mortality has decreased over the years, premature death due to ischemic heart disease remains high.Peer reviewe

The Long-Term Incidence of Hospitalization for Ketoacidosis in Adults with Established T1D-A Prospective Cohort Study

CONTEXT: The long-term natural history of diabetic ketoacidosis (DKA) and its risk factors are poorly understood. OBJECTIVE: To determine the long-term incidence and predictors of DKA in adults with longstanding type 1 diabetes (T1D). DESIGN: All hospitalizations and deaths due to DKA between 1996 and 2016 were identified in 4758 adults with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane), and a cohort of 16 224 adults with T1D from the Finnish general population. RESULTS: Between 1996 and 2015, there were 1228 DKA events in the FinnDiane participants (1.4/100 person-years) and 4914 DKA events (1.8/100 person-years) in adults with T1D from the general population. The majority were hospitalized only once. There was a modest increase in the frequency of DKA in the FinnDiane over the follow-up (~2.4%/year [95% CI, 0.3-4.5%]; P = 0.03). Predictors of DKA were glucose control, CSII, smoking and alcohol consumption, and raised high-density lipoprotein cholesterol and triacylglycerides. Diabetic nephropathy and renal impairment were associated with DKA; patients with end-stage renal disease, macroalbuminuria, and microalbuminuria had 2.09-fol (95% CI, 1.40-3.12), 1.65-fold (95% CI, 1.23-2.19), and 0.87-fold (95% CI, 0.61-1.24) risk of DKA compared with patients with normal albumin excretion rate, respectively. Patients with an estimated glomerular filtration ratePeer reviewe

Metabolomic profile predicts development of microalbuminuria in individuals with type 1 diabetes

Elevated urinary albumin excretion (microalbuminuria) is an early marker of diabetic nephropathy, but there is an unmet need for better biomarkers that capture the individuals at risk with higher accuracy and earlier than the current markers do. We performed an untargeted metabolomic study to assess baseline differences between individuals with type 1 diabetes who either developed microalbuminuria or remained normoalbuminuric. A total of 102 individuals progressed to microalbuminuria during a median follow-up of 3.2 years, whereas 98 sex-, age- and body mass index (BMI) matched nonprogressors remained normoalbuminuric during a median follow-up of 7.1 years. Metabolomic screening identified 1,242 metabolites, out of which 111 differed significantly between progressors and non-progressors after adjustment for age of diabetes onset, baseline glycosylated hemoglobin A1c (HbA(1c)), and albumin excretion rate (AER). The metabolites that predicted development of microalbumiuria included several uremic toxins and carnitine metabolism related molecules. Iterative variable selection indicated erythritol, 3-phenylpropionate, and N-trimethyl-5-aminovalerate as the best set of variables to predict development of microalbuminuria. A metabolomic index based on these metabolites improved the prediction of incident microalbuminuria on top of the clinical variables age of diabetes onset, baseline HbA1c and AER (ROCAUC = 0.842 vs 0.797), highlighting their ability to predict early-phase diabetic nephropathy.Peer reviewe

Nut Consumption Is Associated with Lower Risk of Metabolic Syndrome and Its Components in Type 1 Diabetes

Although nut consumption has been associated with several health benefits, it has not been investigated in individuals with type 1 diabetes. Therefore, our aim was to assess nut consumption and its association with metabolic syndrome in adult individuals with type 1 diabetes taking part in the Finnish Diabetic Nephropathy Study. The nut intake of the 1058 participants was assessed from 3-day food records that were completed twice, and the number of weekly servings, assuming a serving size of 28.4 g, was calculated. Metabolic syndrome was defined as the presence of ≥3 of the cardiovascular risk factors: central obesity, high blood pressure (≥130/85 mmHg or use of antihypertensive medication), high triglyceride concentration (≥1.70 mmol/L or use of lipid-lowering medication), low HDL-cholesterol concentration (7.5%) was used as a criterion for suboptimal glycaemic control. Of the 1058 (mean age 46 years, 41.6% men) participants, 689 (54.1%) reported no nut intake. In the remaining sample, the median weekly nut intake was 40.8 g. In the adjusted models, higher nut intake, as the continuous number of weekly servings and the comparison of those wit