Intraglomerular Dysfunction Predicts Kidney Failure in Type 2 Diabetes

10.2337/figshare.14932734.v1 ◽

2021 ◽

Author(s):

Pierre J Saulnier ◽

Helen C Looker ◽

Michael Mauer ◽

Behzad Najafian ◽

Elise Gand ◽

...

Keyword(s):

Type 2 Diabetes ◽

Latent Class ◽

Renal Plasma Flow ◽

Rapid Decline ◽

Data Link ◽

Arteriolar Tone ◽

End Stage ◽

Intraglomerular Pressure

No longitudinal data link intraglomerular hemodynamic dysfunction with end-stage kidney disease (ESKD) in people with type 2 diabetes (T2D). Afferent (RA) and efferent (RE) arteriolar tone and intraglomerular pressure (PGLO) are not directly measurable in humans but are estimable from glomerular filtration rate (GFR), renal plasma flow (RPF), blood pressure, hematocrit, and plasma oncotic pressure. We examined the association of the RA/RE ratio and PGLO with ESKD incidence in 237 Pima Indian persons with T2D who underwent serial measures of GFR (iothalamate) and RPF (p-aminohippurate). Their association with kidney structural lesions was also examined in a subset of 111 participants. Of the 237 participants (mean age 42 years, diabetes duration 11 years, GFR 153 ml/min, median ACR 36 mg/g), 69 progressed to ESKD during median follow-up of 17.5 years. In latent class analysis, distinct trajectories characterized by increasing RA/RE ratio (HR: 4.60, 95% CI 2.55-8.31) or elevated PGLO followed by a rapid decline (HR: 2.96, 95% CI 1.45-6.02) strongly predicted incident ESKD. PGLO (R2=21%, p<0.0001) and RA/RE (R2=15%, p<0.0001) also correlated with mesangial fractional volume, a structural predictor of DKD progression. In conclusion, intraglomerular hemodynamic parameters associated strongly with incident ESKD and correlated with structural lesions of DKD.

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Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register

Diabetologia ◽

10.1007/s00125-021-05613-1 ◽

2021 ◽

Author(s):

Feifei Cheng ◽

Andrea O. Luk ◽

Hongjiang Wu ◽

Claudia H. T. Tam ◽

Cadmon K. P. Lim ◽

...

Keyword(s):

Type 2 Diabetes ◽

Hong Kong ◽

Kidney Disease ◽

Telomere Length ◽

Rapid Decline ◽

End Stage Kidney Disease ◽

End Stage ◽

Diabetes Register

Abstract Aims/hypothesis Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p < 0.001) than the non-progressors (n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p < 0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p < 0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). Conclusions/interpretation rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract

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Long-term BMI change trajectories in Chinese adults and its association with the hazard of type 2 diabetes: evidence from a 20-year China Health and Nutrition Survey

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000879 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000879

Author(s):

Baibing Mi ◽

Chenlu Wu ◽

Xiangyu Gao ◽

Wentao Wu ◽

Jiaoyang Du ◽

...

Keyword(s):

Type 2 Diabetes ◽

Latent Class ◽

Chinese Adults ◽

Change Trajectories ◽

Nutrition Survey ◽

Health And Nutrition ◽

Increased Risk

IntroductionTo investigate the relationship between long-term change trajectory in body mass index (BMI) and the hazard of type 2 diabetes among Chinese adults.Research design and methodsData were obtained from the China Health and Nutrition Survey (CHNS). Type 2 diabetes was reported by participants themselves in each survey wave. The duration of follow-up was defined as the period from the first visit to the first time self-reported type 2 diabetes, death, or other loss to follow-up from CHNS. The patterns of change trajectories in BMI were derived by latent class trajectory analysis method. The Fine and Gray regression model was used to estimate HRs with corresponding 95% CIs for type 2 diabetes.ResultsFour patterns of the trajectories of change in BMI were identified among Chinese adults, 42.7% of participants had stable BMI change, 40.8% for moderate BMI gain, 8.9% for substantial BMI gain and 7.7% for weight loss. During the follow-up with mean 11.2 years (158 637 person-years contributed by 14 185 participants), 498 people with type 2 diabetes (3.7%) occurred. Risk of type 2 diabetes was increased by 47% among people who gained BMI more substantially and rapidly (HR: 1.47, 95% CI 1.08 to 2.02, p=0.016) and increased by 20% among those in people with the moderate BMI gain (HR: 1.20, 95% CI 0.98 to 1.48, p=0.078), compared with those with stable BMI change.ConclusionsLong-term substantial gain of BMI was significantly associated with an increased risk of type 2 diabetes in the Chinese adults.

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Long-term effectiveness of a community-based model of care in Māori and Pacific patients with type 2 diabetes and chronic kidney disease: a 4-year follow up of the DElay Future End Stage Nephropathy due to Diabetes (DEFEND) study

Internal Medicine Journal ◽

10.1111/imj.12788 ◽

2015 ◽

Vol 45 (8) ◽

pp. 843-849 ◽

Cited By ~ 2

Author(s):

J. Tan ◽

P. Manley ◽

G. Gamble ◽

J. Collins ◽

W. Bagg ◽

...

Keyword(s):

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Model Of Care ◽

Community Based ◽

End Stage

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Defective Nitric Oxide Production and Functional Renal Reserve in Patients with Type 2 Diabetes Who Have Microalbuminuria of African and Asian Compared with White Origin

Journal of the American Society of Nephrology ◽

10.1681/asn.v12102125 ◽

2001 ◽

Vol 12 (10) ◽

pp. 2125-2130

Author(s):

KENNETH ANTHONY EARLE ◽

SEEMA MEHROTRA ◽

RAYMOND NEIL DALTON ◽

ELIZABETH DENVER ◽

RAMASAMYIYER SWAMINATHAN

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Renal Disease ◽

Glomerular Filtration ◽

Plasma Flow ◽

Renal Plasma Flow ◽

Nitric Oxide Production ◽

Oxide Production ◽

End Stage

Abstract. Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m2; P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m2; P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73m2 and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.

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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.

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