Advertisement

Topics

Effect of a Basal/Pre-Meal Insulin Strategy (Detemir/Aspart) on Insulin Secretion and Action in Type 2 Diabetes

2014-08-27 03:18:33 | BioPortfolio

Summary

The optimal insulin therapy in T2DM is controversial and its impact on nonalcoholic fatty liver disease (or NAFLD, a common condition in T2DM; Cusi K, Current Diabetes Reports 2009) has not been systematically studied before, and in particular, never when using the new insulin formulations detemir (Levemir®) or aspart (Novolog®). This study was to determine the effect on hepatic steatosis and insulin secretion/action of lowering the fasting plasma glucose (FPG) to target with once daily basal insulin detemir alone or combining insulin detemir with premeal insulin aspart in patients with uncontrolled type 2 diabetes mellitus (T2DM).

In the first 3 months the investigators will optimize metabolic control in all patients with intensive basal (bedtime) detemir insulin aiming at a normal fasting plasma glucose. After this treatment period, patients will be randomized in the second 3 months in a 2:1 ratio to insulin detemir or detemir plus aspart. The investigators propose that insulin will improve day-long glycemic control and A1c, reduce hepatic steatosis (NAFLD) (primary endpoint) and insulin secretion/sensitivity being well tolerated while causing minimal weight gain and hypoglycemia (secondary endpoints). The study will allow to assess if there is an additional benefit of adding pre-meal rapid-acting insulin aspart to basal insulin to these endpoints.

Description

Clinical studies suggest that control of hyperglycemia in T2DM ameliorates the metabolic abnormalities of T2DM but whether this improves hepatic steatosis has not been examined carefully with the use of improved insulin formulations (i.e, long-acting insulins detemir or glargine, alone or combined with pre-meal short-acting insulins). Most studies have focused on glycemic control without a careful examination to the underlying mechanisms, with some studies reporting on improved hepatic and muscle insulin sensitivity. We have found in our laboratory that intensified insulin therapy in T2DM is associated with enhanced glycogen synthase fractional velocity and non-oxidative glucose disposal, but with no improvement at the level of insulin-stimulated insulin receptor tyrosine phosphorylation, hexokinase II mRNA or enzyme function, phosphatidylinositol 3-kinase (PI 3-kinase) associated with IRS-1, or Akt phosphorylation. Our work did not examine hepatic steatosis or insulin secretion/action, nor was designed to distinguish between the relative contribution of reduced glucotoxicity on insulin sensitivity vs. beta-cell function from pre-meal regular vs. NPH insulin. It is possible that the beneficial effects of insulin therapy of reduced plasma glucose and FFA concentrations may be offset by excessive hyperinsulinemia and weight gain from the use of insulins with suboptimal pharmacokinetics compared to the newer insulin formulations.

Insulin detemir is an insulin analogue approved in 2005 by the FDA. It is a long-acting insulin analogue that has shown to be more predictable in achieving therapeutic plasma insulin levels compared to NPH insulin (see attached articles). This is associated with several clinical benefits, such as better glycemic control, less hypoglycemia, modest weight gain and better quality of life for patients with type 2 diabetes. If gluco-lipotoxicity likely play an important role in the development of hepatic steatosis (NAFLD) in T2DM (as suggested by a growing body of literature, see Cusi K, Current Diabetes Reports 2009) we speculate that if reversed by a strategy of basal long-acting insulin (i.e., insulin detemir) alone, or combined with a rapid-acting analog (i.e., pre-meal insulin aspart) may be a good strategy for the treatment of T2DM. However, the effects of intensive insulin therapy on NAFLD in T2DM (measured by the gold-standard magnetic resonance and spectroscopy or MRS) or on insulin action and insulin secretion using gold-standard metabolic techniques.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Type 2 Diabetes

Intervention

Long-acting bedtime insulin detemir (Levemir), Insulin detemir and pre-meal insulin aspart.

Location

The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital
San Antonio
Texas
United States
78229-3900

Status

Recruiting

Source

The University of Texas Health Science Center at San Antonio

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:18:33-0400

Clinical Trials [3027 Associated Clinical Trials listed on BioPortfolio]

Observational Study on the Weight Effect of Insulin Detemir (Levemir®) in Type 2 Diabetics

This study is conducted in Europe. Observational study evaluating the body weight progress during the treatment with insulin detemir (Levemir®) in Type 2 patients, previously treated with...

Comparison of NPH Insulin and Insulin Detemir in Children and Adolescents With Type 1 Diabetes

This trial is conducted in Europe. The aim of this research is to compare the efficacy and safety of treatment with NPH insulin and insulin detemir. You will be treated with either insuli...

Insulin Detemir Compared to Insulin Glargine: Appetite and Calories Consumed in Type 1 Diabetes

Patients with diabetes treated with insulin often gain weight, which may deter patients from adhering to insulin treatment. Detemir is one type of long acting insulin approved by the Food ...

Examination of the Effects of Liraglutide on the Mode of Action of Insulin Detemir

This trial is conducted in the United States. The aim of this clinical trial is to investigate whether chronic liraglutide administration affects the mode of action (pharmacokinetics) of i...

Insulin Detemir Versus NPH Insulin In Hospitalized Patients With Diabetes

High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications. Improved glucose control with insulin injections may improve ...

PubMed Articles [9719 Associated PubMed Articles listed on BioPortfolio]

Biphasic insulin aspart-30 reduces glycemic variability to a greater degree than insulin detemir: A randomized controlled trial of once-daily insulin regimens using continuous glucose monitoring.

We compared the efficacy of insulin detemir and biphasic insulin aspart-30 given in the morning as an add-on to oral hypoglycemic agents (OHAs) in type 2 diabetic patients.

Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in...

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience.

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessar...

Characterisation of insulin analogues therapeutically available to patients.

The structure and function of clinical dosage insulin and its analogues were assessed. This included 'native insulins' (human recombinant, bovine, porcine), 'fast-acting analogues' (aspart, glulisine,...

Effects of insulin analogs as an add-on to metformin on cutaneous microcirculation in type 2 diabetic patients.

A single insulin injection was shown to improve microcirculatory blood flow. Our aim was to examine the effects of 4weeks of insulin therapy by three randomly assigned insulin analog regimens (Detemir...

Medical and Biotech [MESH] Definitions

A recombinant long-acting insulin and HYPOGLYCEMIC AGENT in which a MYRISTIC ACID is conjugated to a LYSINE at position B29. It is used to manage BLOOD GLUCOSE levels in patients with DIABETES MELLITUS.

An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.

Insulin formulation containing substance which delays or retards time period of the absorption of insulin.

A recombinant LONG ACTING INSULIN and HYPOGLYCEMIC AGENT that is used to manage BLOOD GLUCOSE in patients with DIABETES MELLITUS.

A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.

More From BioPortfolio on "Effect of a Basal/Pre-Meal Insulin Strategy (Detemir/Aspart) on Insulin Secretion and Action in Type 2 Diabetes"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...


Searches Linking to this Trial