Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of th…

Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy.

Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary albumin excretion 1141 mg/24 h. Patients with the highest compared with the lowest quartile of urinary N…

Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.RESULTS: Our GWAS meta-analysis included association result…

Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen

Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain(COL4A3)gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definit…

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Abstract Background The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Me…

Urinary adiponectin excretion rises with increasing albuminuria in type 1 diabetes

Urinary adiponectin (u-adiponectin) excretion has been suggested to reflect early glomerular damage. Inspired by this, we studied the levels of u-adiponectin in type 1 diabetic patients with different levels of urinary albumin excretion (UAE).U-adiponectin was analysed by ELISA in type 1 diabetic patients: Fifty-eight with normoalbuminuria (30mg albumin/24h), 43 with persistent microalbuminuria (30-300mg/24h) and 44 with persistent macroalbuminuria (300mg/24h). For comparison, a control group of 55 healthy individuals was included.U-adiponectin increased with increasing levels of UAE (p0.01). U-adiponectin median (interquartile range): Normoalbuminuria 0.38 (0.14-1.31), microalbuminuria 1.1…

40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients.

Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria.We performed a follow-up study, follow-up median (range) 3.5 (1-5) years. At baseline u-NGAL, u-KIM1 and p-FGF23 (ELISA) was measured and patients were followed yearly with estimated(e)-GFR (MDRD) and u-albumin.We included 177 patients (44 women), mean age (SD) 59 (9) years. eGFR 90 (24) ml/min/1.73 m(2) at baseline, u-albumin: median (interquartile range) 104 (39-238) mg/24 h. Patients with levels of u-KIM1 in the highest quartile had a greater decline in eGFR than patients with the lowest quartile 6.0 (5.4) versus 3.2 (5.5) ml/min/1.73 m(2) per ye…

The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.

Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP).A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months.Urinary tubular markers at baseline and after each treatment period (ELISA),…