scholarly journals The Measurement of Insulin Clearance

2020 ◽  
Author(s):  
Francesca Piccinini ◽  
Richard N. Bergman
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Animal Models ◽  
Measurement Methods ◽  
Insulin Clearance ◽  
Molar Ratio ◽  
Fundamental Aspect ◽  
C Peptide ◽  
Increased Risk

Insulin clearance has recently been highlighted as a fundamental aspect of glucose metabolism, as it has been hypothesized that its impairment could be related to an increased risk of developing type 2 diabetes. This review focuses on methods used to calculate insulin clearance: from the early surrogate indices employing C-peptide to insulin molar ratio, to direct measurement methods used in animal models, to modeling-based techniques to estimate the <i>components </i>of insulin clearance (hepatic versus extra-hepatic). The methods are explored and interpreted by critically highlighting advantages and limitations.

scholarly journals The Measurement of Insulin Clearance

2020 ◽  
Author(s):  
Francesca Piccinini ◽  
Richard N. Bergman
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Animal Models ◽  
Measurement Methods ◽  
Insulin Clearance ◽  
Molar Ratio ◽  
Fundamental Aspect ◽  
C Peptide ◽  
Increased Risk

Insulin clearance has recently been highlighted as a fundamental aspect of glucose metabolism, as it has been hypothesized that its impairment could be related to an increased risk of developing type 2 diabetes. This review focuses on methods used to calculate insulin clearance: from the early surrogate indices employing C-peptide to insulin molar ratio, to direct measurement methods used in animal models, to modeling-based techniques to estimate the <i>components </i>of insulin clearance (hepatic versus extra-hepatic). The methods are explored and interpreted by critically highlighting advantages and limitations.

scholarly journals Lower insulin clearance is associated with increased risk of type 2 diabetes in Native Americans

Diabetologia ◽  
2021 ◽  
Author(s):  
Mujtaba H. Shah ◽  
Paolo Piaggi ◽  
Helen C. Looker ◽  
Ethan Paddock ◽  
Jonathan Krakoff ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Native Americans ◽  
Insulin Clearance ◽  
Increased Risk

scholarly journals Antipsychotics and glucose metabolism: how brain and body collide

2019 ◽  
Vol 316 (1) ◽  
pp. E1-E15 ◽  
Author(s):  
Chantel Kowalchuk ◽  
Laura N. Castellani ◽  
Araba Chintoh ◽  
Gary Remington ◽  
Adria Giacca ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Glucose Metabolism ◽  
First Generation ◽  
Clinical Evidence ◽  
Mental Illnesses ◽  
Therapeutic Effects ◽  
Direct Effects ◽  
Increased Risk

Since the serendipitous discovery of the first antipsychotic (AP) drug in the 1950s, APs remain the cornerstone of treatment for schizophrenia. A shift over the past two decades away from first-generation, conventional APs to so-called “atypical” (or 2nd/3rd generation) APs parallels acknowledgment of serious metabolic side-effects associated in particular with these newer agents. As will be reviewed, AP drugs and type 2 diabetes are now inextricably linked, contributing to the three- to fivefold increased risk of type 2 diabetes observed in schizophrenia. However, this association is not straightforward. Biological and lifestyle-related illness factors contribute to the association between type 2 diabetes and metabolic disease independently of AP treatment. In addition, APs have a well-established weight gain propensity which could also account for elevated risk of insulin resistance and type 2 diabetes. However, compelling preclinical and clinical evidence now suggests that these drugs can rapidly and directly influence pathways of glucose metabolism independently of weight gain and even in absence of psychiatric illness. Mechanisms of these direct effects remain poorly elucidated but may involve central and peripheral antagonism of neurotransmitters implicated not only in the therapeutic effects of APs but also in glucose homeostasis, possibly via effects on the autonomic nervous system. The clinical relevance of studying “direct” effects of these drugs on glucose metabolism is underscored by the widespread use of these medications, both on and off label, for a growing number of mental illnesses, extending safety concerns well beyond schizophrenia.

scholarly journals Animal Models of GWAS-Identified Type 2 Diabetes Genes

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Gabriela da Silva Xavier ◽  
Elisa A. Bellomo ◽  
James A. McGinty ◽  
Paul M. French ◽  
Guy A. Rutter
Keyword(s):  
Type 2 Diabetes ◽  
Animal Models ◽  
Mouse Models ◽  
Human Genetics ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Risk Genes ◽  
Genome Wide ◽  
Increased Risk

More than 65loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notablyTCF7L2andZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.

scholarly journals Association of low fasting C-peptide levels with cardiovascular risk, visit-to-visit glucose variation and severe hypoglycemia in the Veterans Affairs Diabetes Trial (VADT)

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Juraj Koska ◽  
Daniel S. Nuyujukian ◽  
Gideon D. Bahn ◽  
Jin J. Zhou ◽  
Peter D. Reaven
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Decision Making ◽  
Severe Hypoglycemia ◽  
Clinical Decision ◽  
Veterans Affairs ◽  
Cvd Risk ◽  
C Peptide ◽  
Increased Risk ◽  
Control Patterns

Abstract Aims Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia. Materials and methods Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants. Results There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (< 0.50 nmol/l, HR 1.30 [95%CI 1.05–1.60], p = 0.02) and with rising levels in the high range (> 1.23 nmol/l, 1.27 [1.00–1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60–0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate − 0.12 [SE 0.01]; ARV, − 0.10 [0.01]) (p < 0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17–1.87, p = 0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV. Conclusions Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.

scholarly journals The Correlation between Dietary Selenium Intake and Type 2 Diabetes: A Cross-Sectional Population-Based Study on North Chinese Adults

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Sultan Mehmood Siddiqi ◽  
Changhao Sun ◽  
Xiaoyan Wu ◽  
Imranullah Shah ◽  
Anam Mehmood
Keyword(s):  
Type 2 Diabetes ◽  
Logistic Regression ◽  
Glucose Metabolism ◽  
Linear Trend ◽  
Multivariate Logistic Regression Analysis ◽  
Cluster Sampling ◽  
Chinese Adults ◽  
Anthropometric Measures ◽  
Increased Risk

The relationship between selenium (Se) and type 2 diabetes (T2D) remains controversial. In previous animal and cell studies, Se was found to be insulin mimic and antidiabetic, whereas recent epidemiological and interventional trials have shown an unexpected association between high Se intake and increased risk of T2D. The present study aimed to investigate the significance of dietary Se and T2D in North Chinese adults. A large sample of the population was enrolled through cluster sampling in Northern China (N=8824). Information on basic characteristics, anthropometric measures, and dietary Se intake was collected from each subject for analysis. Multivariable logistic regression was used to investigate the association between dietary Se and T2D through adjusted odds ratio (OR) and the corresponding 95% confidence interval (CI). The average nutritional Se intake was 52.43 μg/day, and the prevalence of T2D was 20.4% in the studied population. The OR for developing T2D was 1.66 (95% CI: 1.38, 1.99; P for linear trend <0.005), comparing the highest to the lowest quintile of energy-adjusted Se intake in multivariate logistic regression analysis. The mediation analysis discovered that glucose metabolism (indicated by FBG and HbA1c) mediated this association. In conclusion, our research adds further support to the role of high dietary Se in the incidence of T2D. The results also suggested that this association was mediated by glucose metabolism.

scholarly journals Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study

2011 ◽  
Vol 29 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Melinda L. Irwin ◽  
Catherine Duggan ◽  
Ching-Yun Wang ◽  
Ashley Wilder Smith ◽  
Anne McTiernan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Cox Regression ◽  
Treatment Strategies ◽  
Breast Cancer Diagnosis ◽  
C Peptide ◽  
Risk Of Death ◽  
Increased Risk ◽  
Health Eating

Purpose To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. Patients and Methods This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Results Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m2, women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Conclusion Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored.

scholarly journals The Effect of Sodium-Glucose Cotransporter 2 Inhibitor Ipragliflozin on Insulin Resistance, Hepatic Insulin Clearance, Beta-Cell Function in the Japanese Patients with type 2 Diabetes

2021 ◽  
Author(s):  
Tsuyoshi Okura ◽  
Yohei Fujioka ◽  
Risa Nakamura ◽  
Sonoko Kitao ◽  
Yuichi Ito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Composition ◽  
Beta Cell Function ◽  
Cell Function ◽  
Insulin Clearance ◽  
C Peptide ◽  
Sodium Glucose Cotransporter ◽  
Hepatic Insulin Clearance

Abstract Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a medication for type 2 diabetes mellitus (T2DM). Some reports showed SGLT2i improved insulin resistance, however, the effect on insulin resistance is not well established. Hepatic insulin clearance (HIC) is new pathophysiology of T2DM. The effect of SGLT2i on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i on insulin resistance, insulin secretion, incretins, body composition, and hepatic insulin clearance. Materials and Methods: We conducted a meal tolerance test (MTT), and the hyperinsulinemic-euglycemic clamp in 9 T2DM patients. 50 mg/day ipragliflozin was admitted, MTT and clamp were performed after 4 months. We calculated the postprandial C-peptide AUC to insulin AUC ratio as the HIC. We also measured GLP1, GIP, and glucagon levels during MTT. Results: Body weight, HbA1c, and body composition were not significantly changed after 4 months of treatment. Postprandial glucose, fasting, and postprandial insulin were significantly decreased. The insulin resistance of the glucose clamp was not changed, but HOMA-IR and insulin sensitivity index (ISI) were significantly improved. Incretins and glucagon were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. Fib 4 index and fatty liver index were significantly reduced. HOMA-beta and insulinogenic index was not changed but the C-peptide index was significantly increased. Conclusions: Although patients’ number was small, these results suggest that SGLT2i treatment decreased hepatic insulin resistance, increased hepatic insulin clearance, and decreased hyperinsulinemia, it might protect beta-cell function.

scholarly journals Metabolic and Nutritional Characteristics in Middle-Aged and Elderly Sarcopenia Patients with Type 2 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Qinghua He ◽  
Xiuzhi Wang ◽  
Caizhe Yang ◽  
Xiaoming Zhuang ◽  
Yanfen Yue ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
Glucose Metabolism ◽  
Muscle Strength ◽  
Nutritional Status ◽  
Muscle Mass ◽  
Muscle Quality ◽  
Diabetic Patients ◽  
Increased Risk

Sarcopenia is considered to be a new complication of type 2 diabetes (T2DM) leading to increased risk of adverse outcome. We performed a survey to evaluate glucose metabolism and nutritional status in sarcopenia patients with T2DM. Diabetic participants aged ≥50 years were grouped into a probable sarcopenia group with low muscle strength ( n = 405 ) and a nonsarcopenia group with normal muscle strength ( n = 720 ) according to the revised recommendations from EWGSOP2 (2018). Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, longer diabetes duration, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate and lower bone mineral content, lower fatless upper arm circumference, lower appendicular skeletal muscle mass index (ASMI), and muscle quality in both genders. Multivariable logistic regression analysis showed increased age, male, low BMI, and increased HbA1c, combined with diabetic nephropathy and decreased serum albumin levels, were risk factors associated with low muscle strength in diabetes patients. In conclusion, diabetic patients with sarcopenia had worse glucose metabolism and nutritional status, decreased renal function and reduced muscle quality ,and muscle mass with a greater likelihood of osteoporosis, who need an overall health management to improve outcomes. This clinical trial registration is registered with the Chinese Clinical Trial Registry, ChiCTR-EOC-15006901.

scholarly journals Association of Low Fasting C-Peptide Levels With Cardiovascular Risk, Visit-To-Visit Glucose Variation and Severe Hypoglycemia in The Veterans Affairs Diabetes Trial (VADT)

2021 ◽  
Author(s):  
Juraj Koska ◽  
Daniel S. Nuyujukian ◽  
Gideon Bahn ◽  
Jin J. Zhou ◽  
Peter D. Reaven
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Decision Making ◽  
Severe Hypoglycemia ◽  
Clinical Decision ◽  
Veterans Affairs ◽  
Cvd Risk ◽  
C Peptide ◽  
Increased Risk ◽  
Control Patterns

Abstract Aims Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia. Materials and Methods Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants. Results There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range (<0.50 nmol/l, HR 1.30 [95%CI 1.05-1.60], p=0.02) and with rising levels in the high range (>1.23 nmol/l, 1.27 [1.00-1.63], p=0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60-0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate -0.12 [SE 0.01]; ARV, -0.10 [0.01]) (p<0.0001 all). The association of low C-peptide levels with CVD risk was independent of cardiometabolic risk factors (1.48 [1.17-1.87, p=0.001) and remained associated with CVD when tested in the same model with severe hypoglycemia and glucose CV. Conclusions Low C-peptide levels were associated with increased CVD risk in advanced type 2 diabetes. The association was independent of increases in glucose variation or severe hypoglycemia. C-peptide levels may predict future glucose control patterns and CVD risk, and identify phenotypes influencing clinical decision making in advanced type 2 diabetes.

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