Few data are available on the association between serum lipids and insulin secretion (ISEC) in children. We evaluated the association of triglycerides (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) with ISEC in 1150 non-diabetic obese children and adolescents using multivariable robust median regression. The following models were employed: 1) IGI or incAUCR as the ISEC response variable; 2) QUICKI, OGIS, the Stumvoll index or the Matsuda insulin sensitivity index as the insulin sensitivity (ISEN) predictor; 3) TG, HDL-C and LDL-C as the predictors of interest; 4) 120 min-glucose, age, sex and body mass index as confounders. LDL-C and TG were not associated with ISEC in any model. In 3 out of 4 IGI models, an increase of 1 interquartile range (IQR) of HDL-C was associated with a decrease of median incAUCR ranging from -9 (robust 95%CI -17 to -2) to -8 (-14 to -1) pmol/mmol. In 2 out of 4 incAUCR models, an increase of 1 IQR of HDL-C was associated with a decrease of median IGI ranging from -8 (-15 to -1) to -7 (-11 to -2) pmol/mmol. TG and LDL-C are not associated and HDL-C is inversely associated with ISEC in obese children and adolescents.
Giorgio Bedogni, Andrea Mari, Alessandra De Col, Sofia Tamini, Amalia Gastaldelli and Alessandro Sartorio
Jukka Koffert, Henri Honka, Jarmo Teuho, Saila Kauhanen, Saija Hurme, Riitta Parkkola, Vesa Oikonen, Andrea Mari, Andreas Lindqvist, Nils Wierup, Leif Groop and Pirjo Nuutila
Meal ingestion is followed by a redistribution of blood flow (BF) within the splanchnic region contributing to nutrient absorption, insulin secretion and glucose disposal, but factors regulating this phenomenon in humans are poorly known. The aim of the present study was to evaluate the organ-specific changes in BF during a mixed-meal and incretin infusions.
A non-randomized intervention study of 10 healthy adults to study splanchnic BF regulation was performed.
Effects of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) infusions and mixed-meal were tested in 10 healthy, glucose tolerant subjects using PET-MRI multimodal imaging technology. Intestinal and pancreatic BF and blood volume (BV) were measured with 15O-water and 15O-carbon monoxide, respectively.
Ingestion of a mixed-meal led to an increase in pancreatic and jejunal BF, whereas duodenal BF was unchanged. Infusion of GIP and GLP-1 reduced BF in the pancreas. However, GIP infusion doubled blood flow in the jejunum with no effect of GLP-1.
Together, our data suggest that meal ingestion leads to increases in pancreatic BF accompanied by a GIP-mediated increase in jejunal but not duodenal blood flow.
Henri Honka, Jukka Koffert, Saila Kauhanen, Nobuyuki Kudomi, Saija Hurme, Andrea Mari, Andreas Lindqvist, Nils Wierup, Riitta Parkkola, Leif Groop and Pirjo Nuutila
The mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance.
A total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls.
Bariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test.
Early after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.
Taísa A R Vicente, Ívina E S Rocha, Roberto Salvatori, Carla R P Oliveira, Rossana M C Pereira, Anita H O Souza, Viviane C Campos, Elenilde G Santos, Rachel D C Araújo Diniz, Eugênia H O Valença, Carlos C Epitácio-Pereira, Mario C P Oliveira, Andrea Mari and Manuel H Aguiar-Oliveira
Adult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.
We studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.
The prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.
Lifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.