Implications of blood glucose, insulin resistance and β-cell function in impaired glucose tolerance

1998 ◽  
Vol 40 ◽  
pp. S15-S20 ◽  
Author(s):  
Burkhard Göke
2006 ◽  
Vol 155 (1) ◽  
pp. 73-78 ◽  
Author(s):  
B Steffin ◽  
B Gutt ◽  
M Bidlingmaier ◽  
C Dieterle ◽  
F Oltmann ◽  
...  

Object: Treatment with somatostatin analogues (SA) not only inhibits GH secretion but may also impair insulin secretion. In order to evaluate the influence of SA on glucose metabolism, we investigated insulin resistance (IR) and β-cell function, using the recommended combination of homeostatic model assessment of IR (HOMA-IR) and β-cell function (HOMA-β). Design and methods: This is a prospective, cross-sectional study. We measured fasting insulin, blood glucose and IGF-I. Insulin and blood glucose measurements were taken 120 min after an oral glucose tolerance test with 75 g glucose. We studied 51 patients (27 female/24 male, age 54 years (20–75)). Eighteen patients were on Lanreotide Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5 ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. Results: We found no significant influence of disease activity on HOMA-IR and HOMA-β. In the 33 of 51 subjects without any drug treatment, median HOMA-β was 170.4% (36.0–624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-β was found to be significantly lower (84.2% (36.5–346.2%); P = 0.001). Despite this, there was no difference in HOMA-IR in both groups (2.4 (0.7–8.4) vs 2.3 (0.7–6.1); P < 0.001) despite similar insulin values. Conclusion: In conclusion, we found that LA decreases β-cell function significantly without affecting IR. Therefore, we think that insulin secretagogues are probably more effective in the treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin sensitizers.


2010 ◽  
Vol 298 (1) ◽  
pp. E38-E48 ◽  
Author(s):  
Viorica Ionut ◽  
Huiwen Liu ◽  
Vahe Mooradian ◽  
Ana Valeria B. Castro ◽  
Morvarid Kabir ◽  
...  

Human type 2 diabetes mellitus (T2DM) is often characterized by obesity-associated insulin resistance (IR) and β-cell function deficiency. Development of relevant large animal models to study T2DM is important and timely, because most existing models have dramatic reductions in pancreatic function and no associated obesity and IR, features that resemble more T1DM than T2DM. Our goal was to create a canine model of T2DM in which obesity-associated IR occurs first, followed by moderate reduction in β-cell function, leading to mild diabetes or impaired glucose tolerance. Lean dogs ( n = 12) received a high-fat diet that increased visceral (52%, P < 0.001) and subcutaneous (130%, P < 0.001) fat and resulted in a 31% reduction in insulin sensitivity (SI) (5.8 ± 0.7 × 10−4 to 4.1 ± 0.5 × 10−4 μU·ml−1·min−1, P < 0.05). Animals then received a single low dose of streptozotocin (STZ; range 30–15 mg/kg). The decrease in β-cell function was dose dependent and resulted in three diabetes models: 1) frank hyperglycemia (high STZ dose); 2) mild T2DM with normal or impaired fasting glucose (FG), 2-h glucose >200 mg/dl during OGTT and 77–93% AIRg reduction (intermediate dose); and 3) prediabetes with normal FG, normal 2-h glucose during OGTT and 17–74% AIRg reduction (low dose). Twelve weeks after STZ, animals without frank diabetes had 58% more body fat, decreased β-cell function (17–93%), and 40% lower SI. We conclude that high-fat feeding and variable-dose STZ in dog result in stable models of obesity, insulin resistance, and 1) overt diabetes, 2) mild T2DM, or 3) impaired glucose tolerance. These models open new avenues for studying the mechanism of compensatory changes that occur in T2DM and for evaluating new therapeutic strategies to prevent progression or to treat overt diabetes.


2010 ◽  
Vol 89 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Kei Miyakoshi ◽  
Mamoru Tanaka ◽  
Yoshifumi Saisho ◽  
Akira Shimada ◽  
Kazuhiro Minegishi ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4281-4281
Author(s):  
Pacharapan Surapolchai ◽  
Suradej Hongeng ◽  
Samart Pakakasama ◽  
Pat Mahachoklertwattana ◽  
Angkana Winaichatsak ◽  
...  

Abstract Background: The purposes of the study were to determine β-cell function and insulin sensitivity after ALL therapy cessation and the association between genetic polymorphisms of β-cell differentiation genes, TCF7L2 and PAX4, with insulin resistance (β-cell dysfunction) in childhood ALL survivors. Methods: Childhood ALL patients diagnosed during 1997–2004 finished the treatment for at least 6 months. The oral glucose tolerance test and lipid screening were performed. Impaired glucose tolerance and diabetes mellitus (DM) were defined according to WHO criteria. β-cell function was estimated by homeostasis model assessment β-cell (HOMA β-cell) and insulinogenic index (IGI) and insulin sensitivity was estimated by whole body insulin sensitivity index (WBISI). The polymorphisms of TCF7L2 (rs12255372 and rs7903146) and PAX4 (A1186C) were genotyped and assessed for the association between these polymorphisms and the β-cell function and the insulin sensitivity. Results: 126 patients were studied (52 females, 74 males and age at the time of study; 4–20 yrs). 116 patients (92%) had normal glucose tolerance (NGT) while the others 10 patients (8%) had impaired glucose tolerance (IGT). Comparing between IGT and NGT groups respectively, we found statistically significant differences in age at the diagnosis (7.5 and 5.2 yrs, p=0.041), age at the study (14 and 10.3 yrs, p=0.001), the duration of post ALL therapy cessation (43 and 26 months, p=0.015), and insulin sensitivity index (WBISI) (5.75 and 9.52, p<0.001). HOMA β-cell and IGI were not different between NGT and IGT group (190.8 and 139.5, p=0.332; 23.6 and 15.8, p=0.310, respectively). Moreover, 32 of 126 patients (25%) had insulin resistance (modified from the criteria of WBISI in obese children and adolescents). These 32 patients who had insulin resistance demonstrated significant pictures of metabolic syndrome i.e. hypertriglyceridemia (116.6 and 85.4 mg/dL, p=0.036), low HDL-C (43.0 and 48.3 mg/dL, p=0.015), obesity (BMI SDS 1.03 and 0.38, p=0.044) and were also older age at the study (12.8 and 9.9 yrs, p<0.001). The genotype frequencies and allele frequencies of polymorphisms of TCF7L2 and PAX4 genes between IGT and NGT groups and between insulin resistance and nonresistance were not difference (p>0.05). Conclusion: The childhood ALL survivors who had IGT were associated with the longer duration of ALL therapy cessation, the older age at diagnosis and at the time of study, and insulin resistance while β-cell function was still relatively preserved. Long-term childhood ALL survivors have potential risks of IGT, insulin resistance and metabolic syndrome. Our findings with such small representatives are not yet applicable to associate TCF7L2 and PAX4 polymorphisms with the insulin resistance (β-cell dysfunction) in the childhood ALL survivors.


2010 ◽  
Vol 163 (5) ◽  
pp. 775-782 ◽  
Author(s):  
Gang Chen ◽  
Juan Wu ◽  
Yinghua Lin ◽  
Baoying Huang ◽  
Jin Yao ◽  
...  

ObjectiveTo investigate the associations between cardiovascular risk, insulin resistance (IR), β-cell function and thyroid dysfunction in She ethnic minority group in China.MethodsWe enrolled 5080 participants of She ethnicity in this analysis eventually. We measured serum TSH and thyroid peroxidase antibody (TPOAb) concentrations, blood glucose and insulin levels in both fasting and 2-h postprandial states, serum lipid levels, blood pressure (BP), brachial–ankle pulse wave velocity (baPWV), electrophysiological parameters, includingTpeak–Tendinterval (Tp–e), QT interval and height of the R wave in lead aVL (RaVL), and anthropometric parameters.ResultsThe total prevalence of thyroid dysfunction in this population is 12.1%. Hyperthyroid subjects had shorterTp–einterval and QT interval in electrocardiogram (ECG), while hypothyroid subjects had shorterTp–einterval and longer QT interval in ECG than euthyroid subjects. Neither hyperthyroid nor hypothyroid subjects showed significant difference in BP, pulse pressure, and baPWV compared with euthyroid subjects. RaVL was slightly higher in hyperthyroid subjects, though the difference did not reach statistical significance (P=0.08). Subjects with TSH<0.3 mIU/l had higher blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and β-cell function (HOMA-β), whereas subjects with TSH>10 mIU/l had lower insulin, HOMA-IR, and HOMA-β than the reference group. There was a significant negative correlation, albeit weak, between TSH and HOMA-IR, HOMA-β after adjustment for confounding factors.ConclusionsHypothyroid subjects may carry higher cardiovascular risk than euthyroid subjects. Moreover, IR and β-cell function are inversely correlated with TSH, which may be explained by the decreasing insulin-antagonistic effects of thyroid hormones along with increasing TSH.


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