المؤلفون: Faggionato, Edoardo, Schiavon, Michele, Ekhlaspour, Laya, Buckingham, Bruce, Dalla Man, Chiara

المصدر: IEEE Transactions on Biomedical Engineering. 71(3)

مصطلحات موضوعية: Humans, Adult, Middle Aged, Glucose, Diabetes Mellitus, Type 1, Insulin Resistance, Blood Glucose, Blood Glucose Self-Monitoring, Bayes Theorem, Insulin, Hypoglycemic Agents

الوصف: OBJECTIVE: Modeling the effect of meal composition on glucose excursion would help in designing decision support systems (DSS) for type 1 diabetes (T1D) management. In fact, macronutrients differently affect post-prandial gastric retention (GR), rate of appearance (R[Formula: see text]), and insulin sensitivity (S[Formula: see text]). Such variables can be estimated, in inpatient settings, from plasma glucose (G) and insulin (I) data using the Oral glucose Minimal Model (OMM) coupled with a physiological model of glucose transit through the gastrointestinal tract (reference OMM, R-OMM). Here, we present a model able to estimate those quantities in daily-life conditions, using minimally-invasive (MI) technologies, and validate it against the R-OMM. METHODS: Forty-seven individuals with T1D (weight =78±13 kg, age =42±10 yr) underwent three 23-hour visits, during which G and I were frequently sampled while wearing continuous glucose monitoring (CGM) and insulin pump (IP). Using a Bayesian Maximum A Posteriori estimator, R-OMM was identified from plasma G and I measurements, and MI-OMM was identified from CGM and IP data. RESULTS: The MI-OMM fitted the CGM data well and provided precise parameter estimates. GR and R[Formula: see text] model parameters were not significantly different using the MI-OMM and R-OMM (p 0.05) and the correlation between the two S[Formula: see text] was satisfactory ( ρ =0.77). CONCLUSION: The MI-OMM is usable to estimate GR, R[Formula: see text], and S[Formula: see text] from data collected in real-life conditions with minimally-invasive technologies. SIGNIFICANCE: Applying MI-OMM to datasets where meal compositions are available will allow modeling the effect of each macronutrient on GR, R[Formula: see text], and S[Formula: see text]. DSS could finally exploit this information to improve diabetes management.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4zm3c05sTest

المؤلفون: Purnell, Jonathan Q, Johnson, Geoffrey S, Wahed, Abdus S, Dalla Man, Chiara, Piccinini, Francesca, Cobelli, Claudio, Prigeon, Ronald L, Goodpaster, Bret H, Kelley, David E, Staten, Myrlene A, Foster-Schubert, Karen E, Cummings, David E, Flum, David R, Courcoulas, Anita P, Havel, Peter J, Wolfe, Bruce M

المصدر: Diabetologia. 61(5)

مصطلحات موضوعية: Islets of Langerhans, Humans, Diabetes Mellitus, Obesity, Weight Loss, Insulin, Remission Induction, Gastric Bypass, Postoperative Period, Longitudinal Studies, Prospective Studies, Time Factors, Adult, Middle Aged, Female, Male, Incretins, Disposition index, Frequently-sampled intravenous glucose tolerance test, GIP, GLP-1, Gastric bypass, Glucagon, Insulin secretion, Insulin sensitivity, Lipids, Meal test, Proinsulin, Remission, Clinical Sciences, Paediatrics and Reproductive Medicine, Public Health and Health Services, Endocrinology & Metabolism

الوصف: AIMS/HYPOTHESIS:In this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing. METHODS:Forty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of SI, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB. RESULTS:Postoperatively, weight loss and SI-FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabetic participants and increased in the participants with type 2 diabetes. The resulting disposition indices (DIFSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and SI-MM and DIMM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups. CONCLUSIONS/INTERPRETATION:For up to 2 years following RYGB, obese participants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT00433810.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7km8632jTest

المؤلفون: Purnell, Jonathan Q, Johnson, Geoffrey S, Wahed, Abdus S, Dalla Man, Chiara, Piccinini, Francesca, Cobelli, Claudio, Prigeon, Ronald L, Goodpaster, Bret H, Kelley, David E, Staten, Myrlene A, Foster-Schubert, Karen E, Cummings, David E, Flum, David R, Courcoulas, Anita P, Havel, Peter J, Wolfe, Bruce M

المصدر: Diabetologia. 61(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Prevention, Nutrition, Clinical Research, Digestive Diseases, Obesity, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Diabetes Mellitus, Female, Gastric Bypass, Humans, Incretins, Insulin, Islets of Langerhans, Longitudinal Studies, Male, Middle Aged, Postoperative Period, Prospective Studies, Remission Induction, Time Factors, Weight Loss, Disposition index, Frequently-sampled intravenous glucose tolerance test, Gastric bypass, GIP, GLP-1, Glucagon, Insulin secretion, Insulin sensitivity, Lipids, Meal test, Proinsulin, Remission, Paediatrics and Reproductive Medicine, Public Health and Health Services, Endocrinology & Metabolism, Clinical sciences, Public health

الوصف: Aims/hypothesisIn this prospective case-control study we tested the hypothesis that, while long-term improvements in insulin sensitivity (SI) accompanying weight loss after Roux-en-Y gastric bypass (RYGB) would be similar in obese individuals with and without type 2 diabetes mellitus, stimulated-islet-cell insulin responses would differ, increasing (recovering) in those with diabetes but decreasing in those without. We investigated whether these changes would occur in conjunction with favourable alterations in meal-related gut hormone secretion and insulin processing.MethodsForty participants with type 2 diabetes and 22 participants without diabetes from the Longitudinal Assessment of Bariatric Surgery (LABS-2) study were enrolled in a separate, longitudinal cohort (LABS-3 Diabetes) to examine the mechanisms of postsurgical diabetes improvement. Study procedures included measures of SI, islet secretory response and gastrointestinal hormone secretion after both intravenous glucose (frequently-sampled IVGTT [FSIVGTT]) and a mixed meal (MM) prior to and up to 24 months after RYGB.ResultsPostoperatively, weight loss and SI-FSIVGTT improvement was similar in both groups, whereas the acute insulin response to glucose (AIRglu) decreased in the non-diabetic participants and increased in the participants with type 2 diabetes. The resulting disposition indices (DIFSIVGTT) increased by three- to ninefold in both groups. In contrast, during the MM, total insulin responsiveness did not significantly change in either group despite durable increases of up to eightfold in postprandial glucagon-like peptide 1 levels, and SI-MM and DIMM increased only in the diabetes group. Peak postprandial glucagon levels increased in both groups.Conclusions/interpretationFor up to 2 years following RYGB, obese participants without diabetes showed improvements in DI that approach population norms. Those with type 2 diabetes recovered islet-cell insulin secretion response yet continued to manifest abnormal insulin processing, with DI values that remained well below population norms. These data suggest that, rather than waiting for lifestyle or medical failure, RYGB is ideally considered before, or as soon as possible after, onset of type 2 diabetes.Trial registrationClinicalTrials.gov NCT00433810.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7km8632jTest

المؤلفون: Matveyenko, Aleksey V, Liuwantara, David, Gurlo, Tatyana, Kirakossian, David, Dalla Man, Chiara, Cobelli, Claudio, White, Morris F, Copps, Kyle D, Volpi, Elena, Fujita, Satoshi, Butler, Peter C

المصدر: Diabetes. 61(9)

مصطلحات موضوعية: Liver, Portal Vein, Animals, Dogs, Rats, Rats, Sprague-Dawley, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Insulin Resistance, Insulin, Glucokinase, Blood Glucose, Nerve Tissue Proteins, Signal Transduction, Male, Proto-Oncogene Proteins c-akt, Forkhead Transcription Factors, Insulin Receptor Substrate Proteins, Insulin Secretion, Diabetes Mellitus, Experimental, Type 2, Sprague-Dawley, Medical and Health Sciences, Endocrinology & Metabolism

الوصف: Insulin is secreted as discrete insulin secretory bursts at ~5-min intervals into the hepatic portal vein, these pulses being attenuated early in the development of type 1 and type 2 diabetes mellitus (T2DM). Intraportal insulin infusions (pulsatile, constant, or reproducing that in T2DM) indicated that the pattern of pulsatile insulin secretion delivered via the portal vein is important for hepatic insulin action and, therefore, presumably for hepatic insulin signaling. To test this, we examined hepatic insulin signaling in rat livers exposed to the same three patterns of portal vein insulin delivery by use of sequential liver biopsies in anesthetized rats. Intraportal delivery of insulin in a constant versus pulsatile pattern led to delayed and impaired activation of hepatic insulin receptor substrate (IRS)-1 and IRS-2 signaling, impaired activation of downstream insulin signaling effector molecules AKT and Foxo1, and decreased expression of glucokinase (Gck). We further established that hepatic Gck expression is decreased in the HIP rat model of T2DM, a defect that correlated with a progressive defect of pulsatile insulin secretion. We conclude that the physiological pulsatile pattern of insulin delivery is important in hepatic insulin signaling and glycemic control. Hepatic insulin resistance in diabetes is likely in part due to impaired pulsatile insulin secretion.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/14q2d0ccTest