The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime?

Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine.

Diurnal Cycling of Insulin Sensitivity in Type 2 Diabetes: Evidence for Deviation From Physiology at an Early Stage.

Unlabelled: The aim of this study was to establish the contribution of insulin resistance to the morning (a.m.) versus afternoon (p.

One-hundred year evolution of prandial insulin preparations: From animal pancreas extracts to rapid-acting analogs.

The first insulin preparation injected in humans in 1922 was short-acting, extracted from animal pancreas, contaminated by impurities. Ever since the insulin extracted from animal pancreas has been continuously purified, until an unlimited synthesis of regular human insulin (RHI) became possible in the '80s using the recombinant-DNA (rDNA) technique. The rDNA technique then led to the designer insulins (analogs) in the early '90s.

The physiological basis of insulin therapy in people with diabetes mellitus.

Insulin therapy has been in use now for 100 years, but only recently insulin replacement has been based on physiology. The pancreas secretes insulin at continuously variable rates, finely regulated by sensitive arterial glucose sensing. Pancreatic insulin is delivered directlyin the portal blood to insulinize preferentially the liver.

Pharmacokinetic and Pharmacodynamic Head-to-Head Comparison of Clinical, Equivalent Doses of Insulin Glargine 300 units · mL and Insulin Degludec 100 units · mL in Type 1 Diabetes.

Objective: To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL (Gla-300) and degludec 100 units ⋅ mL (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D).

Research Design And Methods: Subjects with T1D ( = 22, 11 men, age 44.3 ± 12.

Greater Suppression of Glucagon, Lipolysis, and Ketogenesis with Insulin Glargine U300 as Compared with Glargine U100 in Type 1 Diabetes Mellitus.

The aim of this study was to establish the effects of clinical doses of Gla-300 versus Gla-100 on suppression of glucagon, lipolysis, and ketogenesis in type 1 diabetes mellitus (T1DM). Eighteen persons with T1DM (age 40 ± 12 years, diabetes duration 26 ± 12 years, body mass index 23.4 ± 2 kg/m, A1C 7.

Pharmacokinetics, Pharmacodynamics, and Modulation of Hepatic Glucose Production With Insulin Glargine U300 and Glargine U100 at Steady State With Individualized Clinical Doses in Type 1 Diabetes.

Objective: This study characterized the pharmacokinetics (PK), pharmacodynamics (PD), and endogenous (hepatic) glucose production (EGP) of clinical doses of glargine U300 (Gla-300) and glargine U100 (Gla-100) under steady-state (SS) conditions in type 1 diabetes mellitus (T1DM).

Research Design And Methods: T1DM subjects ( = 18, age 40 ± 12 years, T1DM duration 26 ± 12 years, BMI 23.4 ± 2 kg/m, A1C 7.

Prevention and Management of Severe Hypoglycemia and Hypoglycemia Unawareness: Incorporating Sensor Technology.

Purpose Of Review: In addition to assisting in achieving improved glucose control, continuous glucose monitoring (CGM) sensor technology may also aid in detection and prevention of hypoglycemia. In this paper, we report on the current scientific evidence on the effectiveness of this technology in the prevention of severe hypoglycemia and hypoglycemia unawareness.

Recent Findings: Recent studies have found that the integration of CGM with continuous subcutaneous insulin infusion (CSII) therapy, a system known as sensor-augmented pump (SAP) therapy, very significantly reduces the occurrence of these conditions by providing real-time glucose readings/trends and automatically suspending insulin infusion when glucose is low (LGS) or, even, before glucose is low but is predicted to soon be low (PLGS).

Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration.

Background: Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus.

Impact of patient and treatment characteristics on glycemic control and hypoglycemia in patients with type 2 diabetes initiated to insulin glargine or NPH: A post hoc, pooled, patient-level analysis of 6 randomized controlled trials.

Background: The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine).

Methods: Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed.

Results: Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: -1.

Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection.

Objective: Crystalline NPH insulin comes in a two-phase solution with either a solvent or a rapid-acting insulin (in premixed formulations) and needs adequate mixing for complete resuspension before injection. The aim of this study was to establish pharmacokinetics (PK) and pharmacodynamics (PD) after injection of appropriately resuspended versus nonresuspended NPH insulin.

Research Design And Methods: PK and PD were assessed after subcutaneous injection of NPH insulin 0.

Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes.

Objective: To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin glargine in type 2 diabetes mellitus (T2DM) after evening versus morning administration.

Research Design And Methods: Ten T2DM insulin-treated persons were studied during 24-h euglycemic glucose clamp, after glargine injection (0.4 units/kg s.

Metabolism of insulin glargine after repeated daily subcutaneous injections in subjects with type 2 diabetes.

Objective: To investigate concentration of plasma insulin glargine after its subcutaneous dosing compared with concentration of its metabolites 1 (M1) and 2 (M2) in subjects with type 2 diabetes.

Research Design And Methods: Nine subjects underwent a 32-h euglycemic glucose clamp study (0.4 units/kg glargine after 1 week of daily glargine administration).

Differential effects of adiposity on pharmacodynamics of basal insulins NPH, glargine, and detemir in type 2 diabetes mellitus.

Objective: To assess the role of adiposity on the pharmacodynamics of basal insulins NPH, detemir, and glargine in type 2 diabetes mellitus (T2DM), as estimated by glucose infusion rate (GIR) and endogenous glucose production (EGP) rate in the euglycemic clamp.

Research Design And Methods: We examined the variables that best predicted GIR and EGP in 32-h clamp studies after treatment with subcutaneous injection of 0.4 units/kg NPH, detemir, and glargine in 18 T2DM subjects (crossover).

Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era.

In physiology, insulin is released continuously by the pancreas at a nearly constant rate between meals and in the fasting state (basal insulin secretion). The pivotal role of basal insulin is to restrain release of glucose from the liver and free fatty acids from adipose tissue, thus preventing hyperglycemia and ketosis. In type 1 diabetes mellitus (T1DM) (absolute insulin deficiency), the replacement of basal insulin is challenging because the currently available pharmacological preparations of long-acting insulin do not exactly reproduce the fine physiology of flat action profile of basal insulin of subjects without diabetes.

Pharmacokinetics and pharmacodynamics of therapeutic doses of basal insulins NPH, glargine, and detemir after 1 week of daily administration at bedtime in type 2 diabetic subjects: a randomized cross-over study.

Objective: To compare the pharmacokinetics and pharmacodynamics of NPH, glargine, and detemir insulins in type 2 diabetic subjects.

Research Design And Methods: This study used a single-blind, three-way, cross-over design. A total of 18 type 2 diabetic subjects underwent a euglycemic clamp for 32 h after a subcutaneous injection of 0.

Hyperglycemia-induced platelet activation in type 2 diabetes is resistant to aspirin but not to a nitric oxide-donating agent.

Objective: Acute, short-term hyperglycemia enhances high shear stress-induced platelet activation in type 2 diabetes. Several observations suggest that platelets in type 2 diabetes are resistant to inhibition by aspirin. Our aim was to assess comparatively the effect of aspirin, a nitric oxide-donating agent (NCX 4016), their combination, or placebo on platelet activation induced by acute hyperglycemia in type 2 diabetes.

Mechanisms of insulin resistance after insulin-induced hypoglycemia in humans: the role of lipolysis.

Objective: Changes in glucose metabolism occurring during counterregulation are, in part, mediated by increased plasma free fatty acids (FFAs), as a result of hypoglycemia-activated lipolysis. However, it is not known whether FFA plays a role in the development of posthypoglycemic insulin resistance as well.

Research Design And Methods: We conducted a series of studies in eight healthy volunteers using acipimox, an inhibitor of lipolysis.

Short-term effects of the long-acting insulin analog detemir and human insulin on plasma levels of insulin-like growth factor-I and its binding proteins in humans.

Objective: The objective of the study was to compare responses of plasma levels of IGF-I and IGF binding proteins (IGFBP-1 and IGFBP-3) induced by human regular insulin (HI) and the long-acting insulin analog detemir (IDet) at doses equivalent with respect to the glucose-lowering effect.

Experimental Design: Ten nondiabetic subjects (six males, four females; age, 36 +/- 7 yr; body mass index, 22.9 +/- 2.