Kidney Function, β-Cell Function and Glucose Tolerance in Older Men

Jia, Ting; Risérus, Ulf; Xu, Hong; Lindholm, Bengt; Ärnlöv, Johan; Sjögren, Per; Cederholm, Tommy; Larsson, Tobias E.; İkizler, T. Alp; Carrero, Juan Jesús

doi:10.1210/jc.2014-3313

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…In a longitudinal follow-up study of older US adults, beta cell function was increased in the presence of increased insulin resistance inherent to CKD, and the risks of glucose intolerance and incident diabetes were not increased [17]. Similar results were also confirmed by Jia et al, who reported that the net balance between insulin sensitivity and beta cell function was preserved [18]. In those on dialysis, increased beta cell function was observed compared with healthy individuals [20].…”

Section: Discussionsupporting

confidence: 60%

“…In a community-based cohort study of 4680 older adults with a normal mean estimated glomerular filtration rate (eGFR) (72.2 ml min −1 1.73 m −2 ), Pham et al reported that lower eGFR was associated with higher fasting insulin concentrations and a lower insulin sensitivity index [17]. In another community-based cohort study in Sweden of 1015 non-diabetic men aged 70-71 years with a median eGFR of 61.3 ml min −1 1.73 m −2 , insulin sensitivity was negatively correlated with kidney function quartiles [18]. By contrast, the prevalence of insulin resistance did not differ between people with CKD and BMI-matched control individuals, and insulin resistance was correlated with BMI and fat mass, but not with eGFR, in a study of 95 non-diabetic people [19].…”

Section: Discussionmentioning

confidence: 98%

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Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study

et al. 2019

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Aims/hypothesis Chronic kidney disease (CKD) is a known complication of diabetes mellitus, and insulin resistance is a well-known complication of CKD. However, there is no consensus in the published data on the association of CKD with incident diabetes. Methods A total of 15,403 people with CKD were identified from the Taiwan National Health Insurance Research Database to determine their risk of incident diabetes compared with that of 15,403 matched individuals without CKD. Fine and Gray regression models using death as a competing risk were performed to calculate adjusted HRs and 95% CIs. Risk factors for incident diabetes in people with CKD were also determined. Results The CKD cohort had a higher incidence rate of diabetes compared with the non-CKD cohort (11.23/1000 person-years vs 8.93/1000 person-years). In the fully adjusted model, CKD was a significant and independent predictor of incident diabetes (adjusted HR 1.204; 95% CI 1.11, 1.31). The influence of CKD on incident diabetes showed consistent results in three levels of sensitivity analysis. In the CKD cohort, the significant risk factors for incident diabetes included increased age, geographical location, hypertension, hyperlipidaemia and gout. Of these, hypertension was associated with the highest risk of developing incident diabetes (adjusted HR 1.682; 95% CI 1.47, 1.93). Conclusions/interpretation People with CKD were at higher risk of developing incident diabetes. People with CKD and hypertension, hyperlipidaemia, increased age or gout and who lived in certain geographical regions of Taiwan were more likely to develop diabetes as a complication compared with people without those characteristics. Keywords Chronic kidney disease. CKD. Competing-risk regression. Incident diabetes mellitus. Insulin resistance. New-onset diabetes mellitus Abbreviations CKD Chronic kidney disease eGFR Estimated glomerular filtration rate ESRD End-stage renal disease

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 98%

Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study

et al. 2019

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“…Earlier studies have shown variable pancreatic β‐cell function in response to IR in ESRD, leading to glucose intolerance . Interestingly, our study could confirm the compensatory relationship between IR and β‐cell function in the early stage of CKD . IR assessed by clamp increased across decreasing kidney function, while β‐cell function was higher, and 2‐h post‐load glucose tolerance was not different.…”

Section: Causesmentioning

confidence: 80%

“…IR assessed by clamp increased across decreasing kidney function, while β‐cell function was higher, and 2‐h post‐load glucose tolerance was not different. We then conclude that increased β‐cell function compensates for loss in insulin sensitivity that accompanies CKD . The causes of IR in CKD are likely complex and multifactorial.…”

Section: Causesmentioning

confidence: 99%

“…We then conclude that increased β-cell function compensates for loss in insulin sensitivity that accompanies CKD. 2 The causes of IR in CKD are likely complex and multifactorial. Some proposed determinants of IR include lifestyle factors, such as obesity, sedentary habits, unhealthy diet, smoking, visceral fat accumulation, adipokine deregulation and accumulation, metabolic acidosis, chronic inflammation, oxidative stress, vitamin D deficiency, anaemia and uremic toxicity, as well as comorbid conditions, for example, hypertension and hyperlipidaemia.…”

Section: Causesmentioning

confidence: 99%

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Insulin resistance in chronic kidney disease

Carrero

2017

Nephrology

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ABSTRACT:This review provides an overview of insulin resistance (IR) in patients with chronic kidney disease (CKD). IR is a pathological state in which target tissues fail to respond normally to insulin. IR is understood as a consequence of CKD and its prevalence rises particularly in advanced CKD stages. Mechanisms leading to IR are complex and multifactorial, involving post-receptor signaling defects, unhealthy lifestyles, metabolic acidosis, inflammation, oxidative stress, vitamin D deficiency, anemia, and uremic toxicity, as shown by human and experimental studies over the last 30 years. Whereas hyperinsulinemic euglycemic clamp is the gold standard, it is unpractical at the bedside, and either estimated IR indices by fasting glucose or insulin and oral glucose tolerance tests (OGTT) provide satisfactory estimates of IR also in patients with CKD. IR is likely to play a key role in the development of cardiometabolic complications, but not all studies associate IR with the risk of cardiovascular events and death. Various interventions at the level of lifestyle modifications, adaptations in dialysis therapy (such as use of icodextrin based solutions) and pharmacological strategies such as thiazolidinediones or vitamin D therapy may improve IR in patient with CKD.

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Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins

2018

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Recent clinical data have demonstrated a defect of insulin secretion in CKD. Several studies highlighted the direct role of some URS (urea, trimethylamine N-oxide (TMAO), p-cresyl sulfate, 3-carboxylic acid 4-methyl-5-propyl-2-furan propionic (CMPF)) in glucose homeostasis abnormalities and diabetes incidence. Gut dysbiosis has been identified as a potential contributor to diabetes and to the production of URS. The complex interplay between the gut microbiota, kidney, pancreas β cell, and peripheral insulin target tissues has brought out new hypotheses for the pathogenesis of CKD and DKD. The characterization of intestinal microbiota and its associated metabolites are likely to fill fundamental knowledge gaps leading to innovative research, clinical trials, and new treatments for CKD and DKD.

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Kidney Function, β-Cell Function and Glucose Tolerance in Older Men

Abstract: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.

Cited by 8 publications

References 37 publications

Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study

Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study

Insulin resistance in chronic kidney disease

Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins

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