scholarly journals Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes

2021 ◽  
Author(s):  
Tatsuya Fukuda ◽  
Ryotaro Bouchi ◽  
Takato Takeuchi ◽  
Kikuko Amo-Shiinoki ◽  
Atsushi Kudo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Short Chain Fatty Acids ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Cellular Plasticity ◽  
Β Cell ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Histological Characteristics ◽  
Design And Methods

<b>OBJECTIVE</b> <p>To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM).</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM were examined.</p> <p><b>RESULTS</b></p> <p>During follow-up (median, 3.19 years), 2 out of 20 PD patients and 16 out of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma GLP-1, and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed pre-existing insulin resistance compared with non-progressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets.</p> <p><b>CONCLUSIONS</b></p> We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with pre-existing insulin resistance is associated with high cellular-plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.

scholarly journals Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes

2021 ◽  
Author(s):  
Tatsuya Fukuda ◽  
Ryotaro Bouchi ◽  
Takato Takeuchi ◽  
Kikuko Amo-Shiinoki ◽  
Atsushi Kudo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Short Chain Fatty Acids ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Cellular Plasticity ◽  
Β Cell ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Histological Characteristics ◽  
Design And Methods

<b>OBJECTIVE</b> <p>To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM).</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM were examined.</p> <p><b>RESULTS</b></p> <p>During follow-up (median, 3.19 years), 2 out of 20 PD patients and 16 out of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma GLP-1, and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed pre-existing insulin resistance compared with non-progressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets.</p> <p><b>CONCLUSIONS</b></p> We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with pre-existing insulin resistance is associated with high cellular-plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.

scholarly journals Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys

2017 ◽  
Vol 38 (06) ◽  
pp. 411-417 ◽  
Author(s):  
Emma Cockcroft ◽  
Craig Williams ◽  
Sarah Jackman ◽  
Neil Armstrong ◽  
Alan Barker
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function ◽  
Method Agreement

AbstractAssessment of plasma insulin and glucose outcomes is important in paediatric studies aimed at reducing future risk of type 2 diabetes and cardiovascular disease. The aims of this study are to determine the between-method agreement and the day-to-day reliability of fasting and oral glucose tolerance test (OGTT)-derived estimates of insulin sensitivity and β-cell function in healthy boys. Fasting and OGTT assesments of insulin resistance and β-cell function were performed on 28 boys (12.3±2.9 years). Measurements were repeated after 1 week (fasting, n=28) and 1 day (OGTT, n=8). Agreement between estimates of insulin resistance and β-cell function was examined using Pearson’s correlation coefficient. Reliability was assessed using change in the mean, Pearson’s correlation coefficient, and typical error expressed as a coefficient of variation (CV). The Matsuda index was positively related with QUICKI (r=0.88, P<0.001) and negatively related to HOMA-IR (r=−0.76, P<0.001). The Cederholm index was not significantly related with fasting estimates of insulin resistance (all r<0.40, P>0.05). For reliability, QUICKI had the lowest CV% for the fasting (4.7%) and the Cederholm index for the OGTT (6.4%) estimates. The largest CV% was observed in fasting insulin (30.8%) and insulinogenic index 30’ (62.5%). This study highlights differences in between-method agreement and day-to-day reliability for estimates of insulin resistance in youth. The low CV supports the use of the FGIR (fasting) and Cederholm (OGTT) indices in this population.

scholarly journals Early Detection of Insulin Sensitivity and β-Cell Function with Simple Tests Indicates Future Derangements in Late Pregnancy

2008 ◽  
Vol 93 (3) ◽  
pp. 876-880 ◽  
Author(s):  
A. Lapolla ◽  
M. G. Dalfrà ◽  
G. Mello ◽  
E. Parretti ◽  
R. Cioni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Early Pregnancy ◽  
Cell Function ◽  
Late Pregnancy ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Β Cell ◽  
Β Cell Function

Abstract Objective: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). Research Design and Methods: The oral glucose tolerance test (OGTT) was performed in 903 women at 16–20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26–30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and β-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. Results: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower β-cell function than ND. During the late visit, GDM2 also showed impaired β-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. Conclusions: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. β-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

Impaired β-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome

2004 ◽  
Vol 287 (2) ◽  
pp. E241-E246 ◽  
Author(s):  
David A. Ehrmann ◽  
Elena Breda ◽  
Matthew C. Corcoran ◽  
Melissa K. Cavaghan ◽  
Jacqueline Imperial ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
Oral Glucose ◽  
Β Cell ◽  
Glucose Levels ◽  
Control Subjects ◽  
And Control

Deterioration in glucose tolerance occurs rapidly in women with polycystic ovary syndrone (PCOS), suggesting that pancreatic β-cell dysfunction may supervene early. To determine whether the compensatory insulin secretory response to an increase in insulin resistance induced by the glucocorticoid dexamethasone differs in women with PCOS and control subjects, we studied 10 PCOS and 6 control subjects with normal glucose tolerance. An oral glucose tolerance test (OGTT) and a graded glucose infusion protocol were performed at baseline and after subjects took 2.0 mg of dexamethasone orally. Basal (Φb), static (Φs), dynamic (Φd), and global (Φ) indexes of β-cell sensitivity to glucose were derived. Insulin sensitivity (Si) was calculated using the minimal model; a disposition index (DI) was calculated as the product of Si and Φ. PCOS and control subjects had nearly identical fasting and 2-h glucose levels at baseline. Φb was higher, although not significantly so, in the PCOS subjects. The Φd, Φs, and Φ indexes were 28, 19, and 20% higher, respectively, in PCOS subjects. The DI was significantly lower in PCOS (30.01 ± 5.33 vs. 59.24 ± 7.59) at baseline. After dexamethasone, control subjects averaged a 9% increase (to 131 ± 12 mg/dl) in 2-h glucose levels; women with PCOS had a significantly greater 26% increase to 155 ± 6 mg/dl. The C-peptide-to-glucose ratios on OGTT increased by 44% in control subjects and by only 15% in PCOS subjects. The accelerated deterioration in glucose tolerance in PCOS may result, in part, from a relative attenuation in the response of the β-cell to the demand placed on it by factors exacerbating insulin resistance.

scholarly journals Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function

2020 ◽  
Vol 318 (3) ◽  
pp. E381-E391 ◽  
Author(s):  
Julie Lacombe ◽  
Omar Al Rifai ◽  
Lorraine Loter ◽  
Thomas Moran ◽  
Anne-Frédérique Turcotte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Cell Function ◽  
Fasting Glucose ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Β Cell

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.

scholarly journals Pharmacological Treatment of Insulin Resistance at Two Different Stages in the Evolution of Type 2 Diabetes: Impact on Glucose Tolerance and β-Cell Function

2004 ◽  
Vol 89 (6) ◽  
pp. 2846-2851 ◽  
Author(s):  
Anny H. Xiang ◽  
Ruth K. Peters ◽  
Siri L. Kjos ◽  
Jose Goico ◽  
Cesar Ochoa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Intervention Group ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Β Cell ◽  
Late Intervention ◽  
Β Cell Function

Abstract The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before vs. at the onset of diabetes on glucose levels and β-cell function. Nondiabetic Hispanic women of Mexican or Central American descent with prior gestational diabetes mellitus (GDM) were randomized to troglitazone (early intervention), 400 mg/d, or placebo (later intervention). Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and β-cell function were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatment strategies on glucose levels and β-cell function. During a mean follow-up of 4.3 yr between baseline and posttrial tests, glucose tolerance (oral glucose tolerance test glucose area, P = 0.04) and insulin resistance (MINMOD SI, P = 0.02) worsened more in women randomized to late intervention (n = 69) than to early intervention (n = 57). Insulin secretion (acute insulin response in the iv glucose tolerance test, P = 0.09) and β-cell compensation for insulin resistance (disposition index, P = 0.07) also tended to worsen more in the late intervention group. Among women in the late intervention group who developed diabetes, oral glucose tolerance test glucose area (P = 0.0001) and β-cell function (P ≤ 0.04) deteriorated significantly during development of diabetes on placebo and then did not change significantly (P &gt; 0.50) during treatment with troglitazone and posttreatment washout. In high-risk Hispanic women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive β-cell dysfunction during the evolution of type 2 diabetes.

scholarly journals The shape of the glucose response curve during an oral glucose tolerance test heralds β–cell function in a large Chinese population

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xinqi Cheng ◽  
Na Yang ◽  
Yuxiu Li ◽  
Qi Sun ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Population ◽  
Response Curve ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Β Cell ◽  
Glucose Response ◽  
Β Cell Function

Abstract Background The shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict β-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population. Methods A total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. Results The shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired β-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group. Conclusion The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

Effects of Different Methods Used to Take Blood Samples on Blood Glucose Measurements

2021 ◽  
pp. 105477382110247
Author(s):  
Eda Ergin ◽  
Ayten Zaybak
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance Test ◽  
Venous Blood ◽  
Tolerance Test ◽  
Capillary Blood ◽  
Oral Glucose ◽  
Blood Samples ◽  
Significant Difference ◽  
Measurement Results ◽  
Quasi Experimental

The purpose of this study is to compare whether or not there is a difference between venous and capillary blood samples in blood glucose measurements and investigate the effects of different aseptic methods used in skin cleaning before collecting blood samples on measurement results. This quasi-experimental study was conducted with 109 patients. The capillary first and second blood drop values taken from the patients after fasting and at 2 hours following 75 g oral glucose tolerance test (OGTT) and capillary and venous blood glucose values were compared. There was no significant difference between the median venous blood glucose value and the capillary second blood drop value taken after wiping the finger with alcohol. There was no significant difference between the first and second blood drop values of capillary blood glucose 2 hours after OGTT.

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