Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy

Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM.

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“…Later studies confirmed the impaired insulin pulsatility of T2DM patients (e.g. [14], [15], [16]; but see [17]).…”

Section: Introductionmentioning

confidence: 82%

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Satin

Butler

et al. 2015

Molecular Aspects of Medicine

199

201

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“…The present data illustrate that the exaggerated GLP-1 response in patients with type 2 diabetes seems to be the main explanation for the improvement in β-cell function after RYGB in response to a meal. Reduced glucotoxicity may play a role in the improved β-cell function after surgery, but it seems to be of minor importance compared with the actions of GLP-1 (40,41). Of note, HOMA-IR was not different between saline and Ex-9 infusion at any visit.…”

Section: Discussionmentioning

confidence: 99%

Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes

et al. 2013

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β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)–specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

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“…Basal insulin based BOT is recommended as the first step of insulin introduction overseas since it is considered as a safe insulin regimen with less hypoglycemia risk, as well as a simple treatment compared with multiple daily insulin injections because it involves only once daily insulin injection [3]. There is a study which suggested that it improved endogenous insulin secretory function by rectifying fasting glucose to near normal level [8].…”

Section: Discussionmentioning

confidence: 99%

Simple Insulin Dose Adjustment Using 3-3-1 Algorithm in Japanese Patients with Type 2 Diabetes: Start Kanazawa Study (Self-Titration Aggressive Algorithm with Glargine Trial)

Furukawa¹,

Yamaaki²,

Fujimoto³

et al. 2016

JDM

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We implemented a 3-3-1 algorithm in order to provide safe and simple self-titration in patients who newly initiated BOT as well as who were already on BOT and evaluated its utility in clinical setting. A total of 46 patients, 21 patients in the newly-initiated group and 25 patients in the existing BOT group performed dose adjustment using 3-3-1 algorithm. HbA1c was significantly improved 4 weeks after the initiation from 8.5% ± 1.2% at baseline to 7.3% ± 0.7% at the final evaluation (p < 0.01, vs. Baseline). The average daily insulin units increased throughout the study period from 10.1 ± 6.7 at baseline to 14.6 ± 8.9 units at the final evaluation. Weight didn't significantly change throughout the study (p = 0.12). The incidents of hypoglycemia were 0.8/month during the insulin dose selfadjustment period and 0.4/month during the follow-up period. The 3-3-1 algorithm using insulin glargine provided a safe and simple dose adjustment and demonstrated its utility in patients who were newly introduced to insulin treatment as well as who were already on BOT.

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Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy

Cited by 15 publications

References 43 publications

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes

Simple Insulin Dose Adjustment Using 3-3-1 Algorithm in Japanese Patients with Type 2 Diabetes: Start Kanazawa Study (Self-Titration Aggressive Algorithm with Glargine Trial)

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