scholarly journals Glucagon Clearance is Preserved in Type 2 Diabetes

Author(s):  
Magnus F.G. Grøndahl ◽  
Asger Lund ◽  
Jonatan I. Bagger ◽  
Tonny S. Petersen ◽  
Nicolai J. Wewer Albrechtsen ◽  
...  

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity<i>. </i>Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T<sub>½</sub>) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed.<i> </i>Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T<sub>½</sub>. Individuals with obesity had neither a significantly decreased MCR, T<sub>½</sub>, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

2021 ◽  
Author(s):  
Magnus F.G. Grøndahl ◽  
Asger Lund ◽  
Jonatan I. Bagger ◽  
Tonny S. Petersen ◽  
Nicolai J. Wewer Albrechtsen ◽  
...  

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity<i>. </i>Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T<sub>½</sub>) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed.<i> </i>Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T<sub>½</sub>. Individuals with obesity had neither a significantly decreased MCR, T<sub>½</sub>, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fuyao Yu ◽  
Bing He ◽  
Li Chen ◽  
Fengzhe Wang ◽  
Haidong Zhu ◽  
...  

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p&lt;0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p&lt;0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p&lt;0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.


2008 ◽  
Vol 87 (7) ◽  
pp. 630-634 ◽  
Author(s):  
C.W. Bassim ◽  
R.S. Redman ◽  
D.J. DeNucci ◽  
K.L. Becker ◽  
E.S. Nylen

Periodontitis and type 2 diabetes are co-morbid conditions, both characterized by infectious susceptibility. We investigated procalcitonin (ProCT) levels in the serum and saliva of persons with periodontitis and type 2 diabetes (n = 20), to determine if these levels are altered by periodontitis activity or by hyperglycemia. Persons with severe periodontitis showed higher levels of salivary-ProCT than did those with moderate periodontitis (241 ± 71 vs. 77 ± 516 pg/mL, p = 0.02) and higher levels than did healthy control individuals (118 ± 26 pg/mL, p = 0.05). Salivary-ProCT levels were correlated with bleeding-on-probing (r = 0.45, p = 0.05), as well as with HgbA1c (r = 0.49, p = 0.03). Salivary levels of ProCT were higher than serum levels for the periodontitis/diabetes group (152 ± 37 vs. 78 ± 17 pg/mL, p = 0.02) and the control group (118 ± 146 vs. 48 ± 17 pg/mL, p = 0.01). Persons with periodontitis and type 2 diabetes have salivary-ProCT levels that reflect their degree of periodontitis activity and hyperglycemia. This study demonstrates, for the first time, the presence of procalcitonin (ProCT), an established serum marker of infection, in saliva.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Beibei Wang ◽  
Juan Du ◽  
Zhao Zhu ◽  
Zhihong Ma ◽  
Songlin Wang ◽  
...  

Background. To investigate the relationships among blood glucose, mixed saliva glucose, and parotid glucose in type 2 diabetes patients and to evaluate the diagnostic and monitoring value of salivary gland glucose in patients with type 2 diabetes (type 2DM). Material and Methods. Thirty patients with type 2DM and 30 healthy age- and sex-matched individuals were included in this study. Glucose levels in unstimulated mixed saliva and in unstimulated parotid saliva were measured by the glucose oxidase peroxidase method. Results. The blood glucose and parotid salivary glucose levels in type 2DM patients were significantly higher than those in the controls (P<0.05). The blood glucose, parotid salivary glucose, and mixed salivary glucose were 7.46±1.44 mmol/L, 0.18±0.19 mmol/L, and 3.17×10-2±2.84×10-2 mmol/L, respectively, in the type 2DM group; the corresponding glucose levels in the control group were 5.56±0.71 mmol/L, 7.70×10-2±6.02×10-2 mmol/L, and 3.47×10-2±2.79×10-2 mmol/L. The parotid salivary and blood glucose levels in type 2DM patients were strongly correlated; the linear regression equation for blood glucose and parotid salivary glucose was Y=6.267X+6.360, with r=0.810. However, mixed salivary glucose levels were not significantly different in the type 2 diabetes group compared with the control group. Conclusion. Our results suggest that parotid salivary glucose has potential as a biomarker to monitor type 2DM and as a painless, noninvasive method for the management of type 2DM.


Author(s):  
Veit Yves Pascal Jacob ◽  
Jörg Felber ◽  
Nicolle Müller ◽  
Christof Kloos ◽  
Ulrich Alfons Müller ◽  
...  

AbstractGastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.


2021 ◽  
Vol 24 (4) ◽  
pp. 7-14
Author(s):  
Aseel Ali Abd Ali Sahib ◽  
◽  
Mohammed I. Hamzah ◽  
Mahmood Shakir Khudhair ◽  
◽  
...  

Background Type 2 Diabetes Mellitus is produced by cell failure of pancreatic cells and insulin resistance and is a disorder in which the amount of sugar in the blood is elevated. Angiopoietin-like protein 4 (ANGPTL4) functions as an inhibitor of lipoprotein lipase, a critical enzyme in lipid metabolism. The aim of this study was to explore if the ANGPTL4 gene's E40K variant and ANGPTL4 serum levels are related to the Body mass index, fasting glucose levels, lipid levels, and glycated hemoglobin.Method75 people were enrolled in this case-control study, 25 of whom had type 2 diabetes mellitus while the other 50 were healthy control subjects. Fasting blood glucose, Lipid profile, Glycated hemoglobin were estimated by Cobas 111 analyzer, BMI (weight, height) was calculated, angiopoietin-like protein 4by anenzyme-linked immune sorbent test kit and TaqMan genotyping-based real-time PCR was used to ascertain ANGPTL4 genotypes. The variant was linked to the risk of Type 2 Diabetes Mellitus and parameters used to quantify the variant were identified. Result Patients in the 30-50 age range with type 2 diabetes and those in the same age group who serve as controls. The control group had a lower level of angiopoietin-like protein 4 (ANGPTL4) than the diabetes group. Patients with T2DM had a substantially (p< 0.0001) greater fasting serum Angiopoietin-like protein 4 level than the control group (135.1±6.70) ng/ml and (62.35±6.4) ng/ml, respectively. The diabetes group has significantly higher fasting serum glucose, lipid profile, and glycated hemoglobin compared with non-diabetics. Serum Angiopoietin-like protein 4 was correlated positively with body mass index. (CC,CT,TT) genotypes of the rs2010871 polymorphism There was a significant difference in frequency of the control group (p =0.0477); however, there was no significant difference in its level of (diabetics, newly diagnosed type 2 diabetic before treatment)p-value (0.7066, 0.5555) respectively Conclusion Serum Angiopoietin-like protein 4 levels are negatively correlated to cholesterol, positively correlated to triglyceride, negatively correlated to HDL, positively correlated to HbA1c, negatively correlated to LDL, negatively correlated to VLDL, negatively correlated to FBS, negatively correlated to BMI. The C>T allele at the ANGPTL4 gene's rs2010871polymorphic locus was linked to a decreased prevalence of Type 2 diabetes.


2015 ◽  
Vol 100 (8) ◽  
pp. 3103-3111 ◽  
Author(s):  
Imre W. K. Kouw ◽  
Stefan H. M. Gorissen ◽  
Nicholas A. Burd ◽  
Naomi M. Cermak ◽  
Annemarie P. Gijsen ◽  
...  

Context: The progressive loss of muscle mass with aging is accelerated in type 2 diabetes patients. It has been suggested that this is attributed to a blunted muscle protein synthetic response to food intake. Objective: The objective of the study was to test the hypothesis that the muscle protein synthetic response to protein ingestion is impaired in older type 2 diabetes patients when compared with healthy, normoglycemic controls. Design: A clinical intervention study with two parallel groups was conducted between August 2011 and July 2012. Setting: The study was conducted at the research unit of Maastricht University, The Netherlands. Intervention, Participants, and Main Outcome Measures: Eleven older type 2 diabetes males [diabetes; age 71 ± 1 y, body mass index (BMI) 26.2 ± 0.5 kg/m2] and 12 age- and BMI-matched normoglycemic controls (control; age 74 ± 1 y, BMI 24.8 ± 1.1 kg/m2) participated in an experiment in which they ingested 20 g intrinsically L-[1-13C]phenylalanine-labeled protein. Continuous iv L-[ring-2H5]phenylalanine infusion was applied, and blood and muscle samples were obtained to assess amino acid kinetics and muscle protein synthesis rates in the postabsorptive and postprandial state. Results: Plasma insulin concentrations increased after protein ingestion in both groups, with a greater rise in the diabetes group. Postabsorptive and postprandial muscle protein synthesis rates did not differ between groups and averaged 0.029 ± 0.003 vs 0.029 ± 0.003%/h1 and 0.031 ± 0.002 vs 0.033 ± 0.002%/h1 in the diabetes versus control group, respectively. Postprandial L-[1-13C]phenylalanine incorporation into muscle protein did not differ between groups (0.018 ± 0.001 vs 0.019 ± 0.002 mole percent excess, respectively). Conclusions: Postabsorptive muscle protein synthesis and postprandial protein handling is not impaired in older individuals with type 2 diabetes when compared with age-matched, normoglycemic controls.


2020 ◽  
Vol 8 (1) ◽  
pp. e001012 ◽  
Author(s):  
Adrian Brown ◽  
Anne Dornhorst ◽  
Barbara McGowan ◽  
Omar Omar ◽  
Anthony R Leeds ◽  
...  

ObjectivesThe management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT.Research design and methodsIn a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL).ResultsMean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference −4.3 kg, 95% CI −6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (−18.6 units, 95% CI −29.2 to –7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01).ConclusionsPatients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success.Trial registration numberISRCTN21335883.


Open Heart ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. e000967 ◽  
Author(s):  
Mauro Tancredi ◽  
Annika Rosengren ◽  
Ann-Marie Svensson ◽  
Aldina Pivodic ◽  
Soffia Gudbjörnsdottir ◽  
...  

ObjectiveThe purpose of the study was to investigate the excess risk of acute myocardial infarction (AMI) and death from coronary artery disease (coronary heart disease, CHD) in relation to age, level of glycaemic control and renal complications in patients with type 2 diabetes.MethodsA total of 431 579 patients with type 2 diabetes mellitus registered in the Swedish National Diabetes Register from 1 January 1998 to 31 December 2012, and 2 173 620 controls from the general population were included. Cox regression was used to study the excess risk of AMI and CHD.ResultsDuring follow-up of 5.1 years in the diabetes group and 5.4 years in the control group, 36 124 (8.4%) and 115 712 (5.3%) CHD events were registered, with corresponding incidence rates/1000 person-years of 14.64 (95% CI 14.49 to 14.79) and 8.73 (95% CI 8.68 to 8.78), respectively. The HR after adjustment for sex and age was 1.67 (1.65–1.69) which was reduced to 1.42 (1.41–1.44) with further adjustment for level of education, country of birth, diabetes duration and comorbidities. The multivariable-adjusted HR for AMI and CHD death with a time-updated glycated haemoglobin level of 6.9% or lower (≤52 mmol/mol) together with normoalbuminuria and estimated glomerular filtration rate ≥60 mL/min for patients with diabetes compared with controls was 0.95 (95% CI 0.92 to 0.98, p<0.001).ConclusionsIn this study, the excess risk of AMI and CHD death was higher for patients with type 2 diabetes compared with controls but converged to that in the general population in patients with on-target HbA1c levels and without renal complications.


Author(s):  
Muwei Li ◽  
Zhenzhou Zhao ◽  
Xuejie Li ◽  
Chuanyu Gao ◽  
Dongdong Jian ◽  
...  

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P<0.001) while it was 0.793 ([0.716-0.871], P<0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P &lt;0.001) and 0.834 ([0.762-0.905], P &lt;0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.


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