Risk factors of hypertensive pregnancies in women with diabetes and the influence on their future life.

Diabetic women carry a 2-4 times increased risk of a hypertensive pregnancy compared to non-diabetic people. This risk is related to presence of diabetic nephropathy, but also poor glycaemic control. Efforts to improve glycaemic control have decreased perinatal morbidity and mortality related to diabetic nephropathy.

[Who will develop diabetic nephropathy?].

While the pathogenetic mechanisms of diabetic nephropathy are not fully known, the greatest risk factors include long duration of diabetes, prolonged poor glucose homeostasis, hypertension, lipid disorders, smoking and male gender. According to family studies, the development of diabetic nephropathy is also influenced by hereditary factors. Two gene loci associated with end-stage nephropathy have been identified in a genome-wide study.

Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes.

Objective: Osteopontin (OPN) is a multifunctional protein suggested to be a player in the arterial disease of patients with type 2 diabetes. However, its role for complications in patients with type 1 diabetes (T1D) is unknown. We therefore investigated the associations between OPN and diabetic vascular complications and all-cause mortality in patients with T1D.

Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals.

Background: A high-fat diet promotes postprandial systemic inflammation and metabolic endotoxemia. We investigated the effects of three consecutive high-fat meals on endotoxemia, inflammation, vascular function, and postprandial lipid metabolism in patients with type 1 diabetes.

Methods: Non-diabetic controls (n = 34) and patients with type 1 diabetes (n = 37) were given three high-caloric, fat-containing meals during one day.

Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease.

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ3 integrin-dependent migration in vitro.

Type 2 diabetes susceptibility gene variants predispose to adult-onset autoimmune diabetes.

Aims/hypothesis: Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA).

Different lipid variables predict incident coronary artery disease in patients with type 1 diabetes with or without diabetic nephropathy: the FinnDiane study.

Objective: To study the ability of lipid variables to predict incident coronary artery disease (CAD) events in patients with type 1 diabetes at different stages of nephropathy.

Research Design And Methods: Patients (n = 3,520) with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were included in the study. During a follow-up period of 10.

Added value of soluble tumor necrosis factor-α receptor 1 as a biomarker of ESRD risk in patients with type 1 diabetes.

Objective: Recent studies have suggested that circulating levels of the tumor necrosis factor-α receptor 1 (sTNFαR1) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified.

Research Design And Methods: Circulating levels of sTNFαR1 were assessed in 429 patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic Nephropathy (FinnDiane) cohort study.

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification.

Aims/hypothesis: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients.

The consequences of failure to achieve targets of guidelines for prevention and treatment of diabetic complications in patients with type 1 diabetes.

To study how the targets of glycemic, blood pressure (BP) and lipid control based on the American Diabetes Association (ADA) guidelines have been implemented, and to assess the risk of cardiovascular events (CVD) and mortality in patients with type 1 diabetes stratified by nephropathy (DN) status. A nationally representative cohort of patients with type 1 diabetes (N = 3,151) from the FinnDiane Study were included. CVD and deaths were identified from the national registers.

Epidemiology and risk factors for diabetic kidney disease.

Prevalence rates of diabetic kidney disease (DKD) are increasing in parallel with the incidence rates of diabetes mellitus. DKD has already become a significant health problem worldwide. Without radical improvements in prevention and treatment, DKD prevalence will continue to climb.

Circulating concentrations of soluble receptor for AGE are associated with age and AGER gene polymorphisms in children with newly diagnosed type 1 diabetes.

Objective: We analyzed the relationship among soluble receptor for advanced glycation end products (sRAGEs), the clinical phenotype, HLA genotype, and risk-associated single nucleotide polymorphisms (SNPs) in the AGER gene in a large population of Finnish children with newly diagnosed type 1 diabetes.

Research Design And Methods: Samples from 2,115 clinically phenotyped children <15 years of age in whom type 1 diabetes was diagnosed and 316 control subjects were analyzed for sRAGEs. Three SNPs of AGER, previously associated with HLA-DR/DQ haplotype independent diabetes risk (rs2070600, rs9469089, and rs17493811), were analyzed in 1,390 affected subjects.

Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes.

Aims/hypothesis: An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes.

Methods: The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER.

Renin-angiotensin-aldosterone-blockade is associated with decreased use of antidepressant therapy in patients with type 1 diabetes and diabetic nephropathy.

Hypertension and depression are frequent comorbidities of diabetes. Studies suggest that antihypertensive medication affecting the renin-angiotensin-aldosterone system (RAAS) might also relieve depression. Whether this is also seen in patients with type 1 diabetes is not known.

Medication among patients with type 1 diabetes and predialytic renal disease.

Aims: To examine use and changes of medication in the three years before start of chronic renal replacement therapy (RRT) among patients with type 1 diabetes, and the association between predialytic medication and survival on RRT.

Methods: We recorded medication of 496 patients with type 1 diabetes before and after start of RRT in 2000-2006 and followed up until death or end of 2009. Data were retrieved from the Finnish Registry for Kidney Diseases and from the FinDM diabetes database.

Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes.

Adiponectin and urinary adiponectin excretions have been ascribed a function in glomerular physiology and seem to indicate vascular disease in diabetes. The aim of this study was to compare the urinary excretion of albumin and adiponectin as predictors for decline of renal function in patients with type 2 diabetes and early kidney disease. Over 141 patients were screened for renal function (estimated GFR, ml/min*1.

Antihypertensive treatment and resistant hypertension in patients with type 1 diabetes by stages of diabetic nephropathy.

Objective: To assess blood pressure (BP) control, antihypertensive treatment, and prevalence of resistant hypertension (RH) in patients with type 1 diabetes stratified by stage of diabetic nephropathy.

Research Design And Methods: This cross-sectional study included a nationally representative cohort of patients with type 1 diabetes (N = 3,678) from the Finnish Diabetic Nephropathy Study (FinnDiane). The data were linked to the Drug Prescription Register to obtain purchases of antihypertensive drugs 6 months prior to the baseline visit.

Incidence of stroke according to presence of diabetic nephropathy and severe diabetic retinopathy in patients with type 1 diabetes.

Objective: Type 1 diabetes is associated with a markedly increased risk of stroke, but only a few studies on the incidence of stroke in type 1 diabetes exist. Therefore, we assessed the incidence of stroke in patients with type 1 diabetes and studied the impact of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR) on this risk.

Research Design And Methods: We studied 4,083 patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study.

Impact of sex and age at onset of diabetes on mortality from ischemic heart disease in patients with type 1 diabetes.

OBJECTIVE To study whether ischemic heart disease (IHD) mortality among patients with type 1 diabetes (T1D) depends on the age at onset of diabetes and whether this effect is sex specific. RESEARCH DESIGN AND METHODS The study examined long-term IHD-specific mortality in a Finnish population-based cohort of patients with early-onset (0-14 years) and late-onset (15-29 years) T1D (n = 17,306). RESULTS During 433,782 person-years of follow-up, 478 deaths from IHD were observed.

Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes.

Sex and genetic variation influence the risk of developing diabetic nephropathy and ESRD in patients with type 1 diabetes. We performed a genome-wide association study in a cohort of 3652 patients from the Finnish Diabetic Nephropathy (FinnDiane) Study with type 1 diabetes to determine whether sex-specific genetic risk factors for ESRD exist. A common variant, rs4972593 on chromosome 2q31.

Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction.

Objective: Preclinical data suggest that linagliptin, a dipeptidyl peptidase-4 inhibitor, may lower urinary albumin excretion. The ability of linagliptin to lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS) inhibition in humans was analyzed by pooling data from four similarly designed, 24-week, randomized, double-blind, placebo-controlled, phase III trials.

Research Design And Methods: A pooled analysis of four completed studies identified 217 subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary albumin-to-creatinine ratio [UACR] of 30-3,000 mg/g creatinine) while receiving stable doses of RAAS inhibitors.

Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney disease.

Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.