Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp

Ahmad, Iram; Zelnick, Leila R.; Robinson, Nicole; Hung, Adriana M.; Kestenbaum, Bryan; Utzschneider, Kristina M.; Kahn, Steven E.

doi:10.1152/ajpendo.00394.2016

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…On the other hand, HOMAbased indices may be a useful method of assessing the state of carbohydrate metabolism in hemodialysis patients [33,34]. The ambiguity of HOMA indices may also be due to a kinetic bias introduced by obesity and chronic kidney disease [35]. Moreover, a true fasting state was probably not really achieved in most patients of this study, leading to increased variability of measured glucose and insulin concentrations and uncertainty of derived HOMA indices.…”

Section: Discussionmentioning

confidence: 96%

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis

Niemczyk

Schneditz

Wojtecka

et al. 2021

Diabetes Research and Clinical Practice

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The disposal of a glucose bolus was studied to identify glucose metabolism in patients with and without type 2 diabetes mellitus (T2DM) during their regular hemodialysis (HD) treatment. Methods: Plasma glucose, insulin, and c-peptide concentrations were measured during a 60 min observation phase following a rapid glucose infusion (0.5 g/kg dry weight). Glucose disposition and elimination rates were determined from kinetic analysis, and insulinogenic index was calculated. Insulin resistance (R HOMA ) was determined by homeostatic model assessment (HOMA). Results: 35 HD patients (14 with T2DM) distinguished by a higher age (median: 70 vs. 55 y, p < 0.01) in T2DM patients were studied. Glucose kinetic data showed only small differences between patients with or without T2DM, but as R HOMA measured in all patients increased, a larger fraction of glucose was removed by the extracorporeal system (r = 0.430, p = 0.01).One hour after glucose bolus injection the glucose level was not different from that before HD also in patients with T2DM (p = 0.115). Conclusions: The larger glucose amount recovered in dialysate in patients with increasing R HOMA indicates that impaired glucose disposal could be measured during HD using a non-invasive dialysis quantification approach without blood sampling. Glucose infusion during HD is safe also in patients with T2DM.

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Section: Discussionmentioning

confidence: 96%

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis

Niemczyk

Schneditz

Wojtecka

et al. 2021

Diabetes Research and Clinical Practice

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“…Serum biomarkers of kidney function were measured in fasting blood. A more detailed description of the study design, recruitment, and enrollment has been published previously 3,14 .…”

Section: Methodsmentioning

confidence: 99%

Impaired incretin homeostasis in non-diabetic moderate-severe CKD

Ahmadi,

Gamboa,

Norman

et al. 2023

Preprint

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BackgroundIncretins are regulators of insulin secretion and glucose homeostasis that are metabolized by dipeptidyl peptidase-4 (DPP-4). Moderate-severe CKD may modify incretin release, metabolism, or response.MethodsWe performed 2-hour oral glucose tolerance testing (OGTT) in 59 people with non-diabetic CKD (eGFR<60 ml/min per 1.73 m2) and 39 matched controls. We measured total (tAUC) and incremental (iAUC) area under the curve of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors.ResultsMean eGFR was 38 ±13 and 89 ±17ml/min per 1.73 m2in CKD and controls. GLP-1 iAUC and GIP iAUC were higher in CKD than controls with a mean of 1531 ±1452 versus 1364 ±1484 pMxmin, and 62370 ±33453 versus 42365 ±25061 pgxmin/ml, respectively. After adjustment, CKD was associated with 15271 pMxmin/ml greater GIP iAUC (95% CI 387, 30154) compared to controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122, 95% CI -619, 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6, 95% CI 0.3, 2.8 mg/dl) and 120 minutes (mean difference, 0.84, 95% CI 0.2, 1.5 mg/dl) in CKD compared to controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups.ConclusionIncretin response to oral glucose is preserved or augmented in moderate-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression are enhanced.Significance statementCKD is associated with metabolic and physiological disturbances including disturbed glucose and insulin homeostasis. Incretin hormones are potent regulators of insulin secretion and glucose metabolism; however, determinants and potential consequence of incretin response in CKD are incompletely understood. This study revealed that total incretin levels and incretin response during oral glucose tolerance testing (OGTT) were significantly higher among patients with moderate-severe non-diabetic CKD compared to healthy. Unlike in healthy individuals, increased incretin response was not correlated with insulin and C-peptide response to OGTT in CKD. These differences coincided with persistently greater glucagon levels in response to physiological stimuli in CKD. Disruption in the incretin system and glucagon dynamics may contribute to metabolic disturbances in moderate-severe CKD.Visual abstract

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“…In a study that evaluated insulin resistance by the insulin sensitivity index suggested that participants with CKD and obesity had a lower insulin sensitivity index [ 71 ]. In contrast, the adjustment for physical activity and diet partially attenuated the associations of CKD with insulin sensitivity and insulin [ 72 ]. The animal study also showed that modulating insulin signal transduction cascades could alleviate the high-fat diet (HFD)-induced insulin resistance and CKD in obese rats [ 73 ].…”

Section: The Mechanism Of Obesity-induced Nephropathymentioning

confidence: 99%

Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

Wang

Chen

et al. 2022

IJMS

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The rapid growth of obesity worldwide has made it a major health problem, while the dramatic increase in the prevalence of obesity has had a significant impact on the magnitude of chronic kidney disease (CKD), especially in developing countries. A vast amount of researchers have reported a strong relationship between obesity and chronic kidney disease, and obesity can serve as an independent risk factor for kidney disease. The histological changes of kidneys in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Furthermore, inflammation, renal hemodynamic changes, insulin resistance and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is no targeted treatment for obesity-related kidney disease. In this review, RAS inhibitors, SGLT2 inhibitors and melatonin would be presented to treat obesity-induced kidney injury. Furthermore, we concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential.

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Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp

Cited by 6 publications

References 39 publications

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis

Impaired incretin homeostasis in non-diabetic moderate-severe CKD

Kidney Damage Caused by Obesity and Its Feasible Treatment Drugs

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