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

2017 ◽  
Vol 312 (3) ◽  
pp. E175-E182 ◽  
Author(s):  
Iram Ahmad ◽  
Leila R. Zelnick ◽  
Nicole R. Robinson ◽  
Adriana M. Hung ◽  
Bryan Kestenbaum ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Insulin Sensitivity ◽  
Kidney Disease ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Euglycemic Clamp ◽  
Insulin Kinetics ◽  
Hyperinsulinemic Euglycemic Clamp ◽  
Sensitivity Indices ◽  
Organ Specific

Insulin sensitivity can be measured by procedures such as the hyperinsulinemic euglycemic clamp or by using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. In a cross-sectional study of 59 subjects with nondiabetic CKD [estimated glomerular filtration rate: (GFR) <60 ml·min−1·1.73 m2] and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SIclamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Mean age was 62.6 yr; 48% of the participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8–38% lower in participants with vs. without CKD and 13–59% lower in obese compared with nonobese participants. Correlations of surrogate indices with SIclamp did not differ significantly by CKD or obesity status. Adjusting for SIclamp in addition to demographic factors, Matsuda index was 15% lower in participants with vs. without CKD ( P = 0.09) and 36% lower in participants with vs. without obesity ( P = 0.0001), whereas 1/HOMA-IR was 23% lower in participants with vs. without CKD ( P = 0.02) and 46% lower in participants with vs. without obesity ( P < 0.0001). We conclude that CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SIclamp, but they do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.

scholarly journals Validation of Steady-State Insulin Sensitivity Indices in Chronic Kidney Disease

Diabetes Care ◽  
2007 ◽  
Vol 30 (7) ◽  
pp. 1813-1818 ◽  
Author(s):  
M. F. Crutchlow ◽  
B. Robinson ◽  
B. Pappachen ◽  
N. Wimmer ◽  
A. J. Cucchiara ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Steady State ◽  
Insulin Sensitivity ◽  
Kidney Disease ◽  
Sensitivity Indices

scholarly journals Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 89
Author(s):  
Jialing Huang ◽  
Marcela Covic ◽  
Cornelia Huth ◽  
Martina Rommel ◽  
Jonathan Adam ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Leptin Receptor ◽  
Adrenal Glands ◽  
Human Study ◽  
Wild Type ◽  
Cross Sectional ◽  
Potential Implication ◽  
Early Biomarkers ◽  
Organ Specific

Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

scholarly journals Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers

2021 ◽  
Author(s):  
Frederico G. S. Toledo ◽  
William F. Martin ◽  
Linda Morrow ◽  
Carine Beysen ◽  
Daiva Bajorunas ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Healthy Volunteers ◽  
Exploratory Study ◽  
The Body ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
C Peptide ◽  
Bipolar I Disorder ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

AbstractA combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.

scholarly journals Contributors, risk associates, and complications of frailty in patients with chronic kidney disease: a scoping review

2019 ◽  
Vol 10 ◽  
pp. 204062231988038 ◽  
Author(s):  
Patrick Yihong Wu ◽  
Chia-Ter Chao ◽  
Ding-Cheng Chan ◽  
Jenq-Wen Huang ◽  
Kuan-Yu Hung
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sociodemographic Factors ◽  
Cross Sectional ◽  
Multifaceted Approach ◽  
Organ Specific ◽  
Health Related ◽  
Stage Renal Disease ◽  
End Stage

Frailty exhibits diverse influences on health-related outcomes and represents a surrogate of increased susceptibility to harmful injuries. Patients with chronic kidney disease (CKD) are at a higher risk of accelerated biologic aging, and, in this population, the concept of frailty emerges as an instrumental measurement of physiologic reserves. However, a comprehensive description of known independent contributors to, and risk associates of, frailty in these patients remain unavailable. In the present review, original studies up to 28 February 2019 that assessed frailty in patients with all stages of CKD were retrieved and reviewed, with results extracted and summarized. By pooling 62 original investigations, 58.1% and 49.1% used cohort and cross-sectional designs, respectively. Dialysis-dependent end-stage renal disease patients ( n = 39; 62.9%) were the most commonly examined population, followed by those with nondialysis CKD ( n = 12; 19.4%) and those receiving renal transplantation ( n = 11; 17.7%). Contributors to frailty in CKD patients included sociodemographic factors, smoking, CKD severity, organ-specific comorbidities, depression, hypoalbuminemia, and low testosterone levels. Conversely, the development of frailty was potentially associated with the emergence of cardiometabolic, musculoskeletal, and cerebral complications; mental distress; and a higher risk of subsequent functional and quality-of-life impairment. Moreover, frailty in CKD patients increased healthcare utilization and consistently elevated mortality among affected ones. Based on the multitude of contributors to frailty and its diverse health influences, a multifaceted approach to manage CKD patients with frailty is needed, and its potential influences on outcomes besides mortality need to be considered.

scholarly journals Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women

2021 ◽  
Author(s):  
Anouar Aznou ◽  
Rick I. Meijer ◽  
Dani�l H van Raalte ◽  
Martin den Heijer ◽  
Annemieke C Heijboer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cross Sectional Study ◽  
Obese Women ◽  
Cross Sectional ◽  
Negatively Associated ◽  
Euglycemic Clamp ◽  
Peripheral Insulin Resistance ◽  
Hyperinsulinemic Euglycemic Clamp

Objective The mechanisms underlying the development of peripheral insulin resistance are complex. Several studies have linked sclerostin, an osteocyte-derived inhibitor of the Wnt/β-catenin pathway, to obesity and insulin resistance. The aim of this study was to investigate 1) whether serum sclerostin is associated with insulin sensitivity in lean and/or obese women; and 2) whether hyperinsulinemia affects serum sclerostin concentrations. Design A cross-sectional study. Methods Insulin sensitivity was measured in lean (BMI<25 kg·m-2) and obese (BMI > 30 kg·m-2) women using a hyperinsulinemic-euglycemic clamp. Serum sclerostin was measured at baseline and during the clamp procedure. Results We studied 21 lean and 22 obese women with a median age of 40 and 43 years and a median BMI of 22.4 and 33.5 kg·m-2, respectively. Obese women had higher serum sclerostin than lean women (122±33 vs 93±33 nmol/L, p<0.01). Higher serum sclerostin was associated with lower insulin sensitivity in obese, but not in lean individuals (difference in M value between highest and lowest quartile: -7.02 mg⋅kg−1⋅min−1, p = 0.03 and 1.59 mg⋅kg−1⋅min−1, p = 0.50, respectively). Hyperinsulinemia did not affect serum sclerostin in lean nor obese women (p>0.5). Conclusion Serum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinemic euglycemic clamp in obese, but not lean women. This indicates a potential role of the Wnt/β-catenin pathway in regulating insulin sensitivity particularly in obese individuals. Our findings remain hypothesis-generating and should be confirmed by additional studies.

scholarly journals The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia

2015 ◽  
Vol 119 (12) ◽  
pp. 1383-1392 ◽  
Author(s):  
S. W. Holwerda ◽  
L. J. Reynolds ◽  
R. M. Restaino ◽  
D. P. Credeur ◽  
H. J. Leidy ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Baroreflex Sensitivity ◽  
Glucose Consumption ◽  
Oral Glucose ◽  
Short Term ◽  
Acute Hyperglycemia ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (<5,000 steps/day). Spontaneous cardiac BRS (sequence technique) was compared at rest and for 120 min following an OGTT at baseline and after RA5. A substudy ( n = 8) was also performed to independently investigate the influence of elevated insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P < 0.001). Resting cardiac BRS was unaffected by RA5 and significantly reduced during the OGTT similarly at baseline and RA5 (baseline 0 min, 28 ± 4 vs. 120 min, 18 ± 4; RA5 0 min, 28 ± 4 vs. 120 min, 21 ± 3 ms/mmHg). Spontaneous cardiac BRS was also reduced during the hyperinsulinemic-euglycemic clamp ( P < 0.05). Collectively, these data demonstrate that acute elevations in plasma glucose and insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity.

HUBUNGAN EFIKASI DIRI DENGAN KUALITAS HIDUP PASIEN GAGAL GINJAL KRONIK YANG MENJALANI HEMODIALISIS

2018 ◽  
Vol 5 (2) ◽  
pp. 56-63
Author(s):  
Abdul Wakhid ◽  
Estri Linda Wijayanti ◽  
Liyanovitasari Liyanovitasari
Keyword(s):  
Quality Of Life ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Self Efficacy ◽  
Healing Process ◽  
Sampling Technique ◽  
P Value ◽  
Cross Sectional ◽  
Kolmogorov Smirnov

Background: Self efficacy can optimize the quality of life of clients who undergo the healing process due to chronic diseases. Individuals with higher self-efficacy move their personal and social resources proactively to maintain and improve the quality and length of their lives so that they experience a better quality of life. Objectives: the purpose of this study was to find the correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency. Metode: This type of research was descriptive correlation with cross sectional approach. The samples in this study more 76 people with total sampling technique. The data collection tool for self efficacy was measured by General Self-Efficacy scale, for quality of life with WHOQoL-BREF. Statistical test used Kolmogorov-smirnov. Result: The result showed that self efficacy in patients with chronic kidney disease was mostly in moderate category (53,9%), quality of life in patients with chronic kidney disease was mostly in good category (68,4%). There was a correlation between self efficacy and quality of life of patients with chronic kidney disease who undergo hemodialysis at RSUD Semarang Regency, the result obtained p-value of 0.000 <α (0,05). Suggestion: Patients with chronic kidney disease can maintain good quality of life by helping to generate positive self-esteem and high self efficacy.

scholarly journals Elevated alanine aminotransferase and low aspartate aminotransferase/alanine aminotransferase ratio are associated with chronic kidney disease among middle-aged women: a cross-sectional study

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hirotaka Ochiai ◽  
Takako Shirasawa ◽  
Takahiko Yoshimoto ◽  
Satsue Nagahama ◽  
Akihiro Watanabe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Venous Blood ◽  
Cross Sectional Study ◽  
Middle Aged ◽  
Cross Sectional ◽  
Alcoholic Fatty Liver ◽  
Relationship Of

Abstract Background Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan. Methods The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD. Results “Elevated ALT and elevated GGT” and “elevated ALT and non-elevated GGT” significantly increased the OR for CKD when compared with “non-elevated ALT and non-elevated GGT” (OR: 2.56, 95% CI: 2.10–3.12 and OR: 2.24, 95% CI: 1.81–2.77). Compared with “AST/ALT ratio ≥ 1 and non-elevated GGT”, “AST/ALT ratio < 1 and elevated GGT” and “AST/ALT ratio < 1 and non-elevated GGT” significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36–3.15 and OR: 1.68, 95% CI: 1.52–1.87). These findings still remained after adjustment for confounders. Conclusions Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.

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