Changes in Albuminuria But Not GFR are Associated with Early Changes in Kidney Structure in Type 2 Diabetes

BackgroundIn type 1 diabetes, changes in the GFR and urine albumin-to-creatinine ratio (ACR) are related to changes in kidney structure that reflect disease progression. However, such changes have not been studied in type 2 diabetes.MethodsParticipants were American Indians with type 2 diabetes enrolled in a clinical trial of losartan versus placebo. We followed a subset who underwent kidney biopsy at the end of the 6-year trial, with annual measurements of GFR (by urinary clearance of iothalamate) and ACR. Participants had a second kidney biopsy after a mean follow-up of 9.3 years. We used quantitative morphometric analyses to evaluate both biopsy specimens.ResultsBaseline measures for 48 participants (12 men and 36 women, mean age 45.6 years) who completed the study included diabetes duration (14.6 years), GFR (156 ml/min), and ACR (15 mg/g). During follow-up, glomerular basement membrane (GBM) width, mesangial fractional volume, and ACR increased, and surface density of peripheral GBM and GFR decreased. After adjustment for sex, age, ACR, and each morphometric variable at baseline, an increase in ACR during follow-up was significantly associated with increases in GBM width, mesangial fractional volume, and mean glomerular volume, and a decrease in surface density of peripheral GBM. Decline in GFR was not associated with changes in these morphometric variables after additionally adjusting for baseline GFR.ConclusionsIn American Indians with type 2 diabetes and preserved GFR at baseline, increasing ACR reflects the progression of earlier structural glomerular lesions, whereas early GFR decline may not accurately reflect such lesions.

Download Full-text

Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial

Diabetes Care ◽

10.2337/dc16-0795 ◽

2016 ◽

Vol 39 (11) ◽

pp. 2004-2010 ◽

Cited By ~ 5

Author(s):

Stephanie K. Tanamas ◽

Pierre-Jean Saulnier ◽

Gudeta D. Fufaa ◽

Kevin M. Wheelock ◽

E. Jennifer Weil ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Kidney Disease ◽

Randomized Clinical Trial ◽

American Indians ◽

Term Effect ◽

Long Term Effect

Download Full-text

Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes

American Journal of Nephrology ◽

10.1159/000481269 ◽

2017 ◽

Vol 46 (4) ◽

pp. 276-284 ◽

Cited By ~ 4

Author(s):

Pierre-Jean Saulnier ◽

Brad P. Dieter ◽

Stephanie K. Tanamas ◽

Sterling M. McPherson ◽

Kevin M. Wheelock ◽

...

Keyword(s):

Type 2 Diabetes ◽

American Indians ◽

Lower Risk ◽

Proportional Hazards ◽

Risk Of Death ◽

Amyloid A ◽

C Statistic ◽

Traditional Risk Factors

Background: Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD. Methods: SAA concentration was measured in serum samples obtained at the start of follow-up. Multivariate proportional hazards models were employed to examine the magnitude of the risk of ESRD or death across tertiles of SAA concentration after adjustment for traditional risk factors. The C statistic was used to assess the additional predictive value of SAA relative to traditional risk factors. Results: Of 256 participants (mean ± SD glomerular filtration rate [iothalamate] = 148 ± 45 mL/min, and median [interquartile range] urine albumin/creatinine = 39 [14-221] mg/g), 76 developed ESRD and 125 died during a median follow-up period of 15.2 and 15.7 years, respectively. After multivariable proportional hazards regression, participants in the 2 highest SAA tertiles together exhibited a 53% lower risk of ESRD (hazard ratio [HR] 0.47, 95% CI 0.29-0.78), and a 30% lower risk of death (HR 0.70, 95% CI 0.48-1.02), compared with participants in the lowest SAA tertile, although the lower risk of death was not statistically significant. Addition of SAA to the ESRD model increased the C statistic from 0.814 to 0.815 (p = 0.005). Conclusions: Higher circulating SAA concentration is associated with a reduced risk of ESRD in American Indians with type 2 diabetes.

Download Full-text

Prospective Associations of Systemic and Urinary Choline Metabolites with Incident Type 2 Diabetes

Clinical Chemistry ◽

10.1373/clinchem.2015.250761 ◽

2016 ◽

Vol 62 (5) ◽

pp. 755-765 ◽

Cited By ~ 31

Author(s):

Gard F T Svingen ◽

Hall Schartum-Hansen ◽

Eva R Pedersen ◽

Per M Ueland ◽

Grethe S Tell ◽

...

Keyword(s):

Type 2 Diabetes ◽

Hdl Cholesterol ◽

Prospective Data ◽

Incident Type ◽

Reactive Protein ◽

Urine Albumin ◽

Net Reclassification Improvement ◽

Incident Type 2 Diabetes

Abstract BACKGROUND Several compounds in the choline oxidation pathway are associated with insulin resistance and prevalent diabetes; however, prospective data are scarce. We explored the relationships between systemic and urinary choline-related metabolites and incident type 2 diabetes in an observational prospective study among Norwegian patients. METHODS We explored risk associations by logistic regression among 3621 nondiabetic individuals with suspected stable angina pectoris, of whom 3242 provided urine samples. Reclassification of patients was investigated according to continuous net reclassification improvement (NRI >0). RESULTS After median (25th to 75th percentile) follow-up of 7.5 (6.4–8.7) years, 233 patients (6.4%) were registered with incident type 2 diabetes. In models adjusted for age, sex, and fasting status, plasma betaine was inversely related to new-onset disease [odds ratio (OR) per 1 SD, 0.72; 95% CI, 0.62–0.83; P < 0.00001], whereas positive associations were observed for urine betaine (1.25; 1.09–1.43; P = 0.001), dimethylglycine (1.22; 1.06–1.40; P = 0.007), and sarcosine (1.30; 1.13–1.49; P < 0.001). The associations were maintained in a multivariable model adjusting for body mass index, hemoglobin A1c, urine albumin-to-creatinine ratio, estimated glomerular filtration rate, C-reactive protein, HDL cholesterol, and medications. Plasma betaine and urine sarcosine, the indices most strongly related to incident type 2 diabetes, improved reclassification [NRI >0 (95% CI) 0.33 (0.19–0.47) and 0.16 (0.01–0.31), respectively] and showed good within-person reproducibility. CONCLUSIONS Systemic and urinary concentrations of several choline metabolites were associated with risk of incident type 2 diabetes, and relevant biomarkers may improve risk prediction.

Download Full-text

Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000190 ◽

2014 ◽

Vol 84 (1-2) ◽

pp. 27-34 ◽

Cited By ~ 7

Author(s):

Nasser M. Al-Daghri ◽

Khalid M. Alkharfy ◽

Nasiruddin Khan ◽

Hanan A. Alfawaz ◽

Abdulrahman S. Al-Ajlan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Serum Levels ◽

Vitamin D Supplementation ◽

Serum Selenium ◽

Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

Download Full-text