Clinical trial NCT00468364: Comparison of Insulin Glargine and NPH Insulin at Night and at Hypoglycemia in Type 2 Diabetes
Official title: Comparison of Carbohydrate Metabolism During the Night and at Hypoglycemia in Type-2 Diabetic Patients Either on Glargine or NPH Insulin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes
Keywords: Hypoglycemia, bedtime insulin, long-acting insulin
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2007-05-02
Enrollment: 12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: DEFINED_POPULATION
Time perspective: OTHER

Brief summary: Long-acting insulin injected at bedtime may cause hypoglycemia (low blood sugar) in the night in patients with diabetes. The aims of the study are 1) to compare the dynamic characteristics of long-acting insulin analog glargine with those of NPH insulin and placebo during the night and the early morning hours, 2) investigate differences on glucose metabolism of bedtime glargine versus NPH insulin at induced hypoglycemia.

Detailed description: Patients with advanced type 2 diabetes like those with type 1 diabetes are at risk for defective glucose counterregulation and hypoglycemia unawareness, the components of hypoglycemia-associated autonomic failure and the resultant vicious cycle of recurrent iatrogenic hypoglycemia. This may explain why iatrogenic hypoglycemia becomes limiting to glycemic control as patients approach the insulin-deficient end of the spectrum of type 2 diabetes. Compared to Neutral Protamin Hagedorn (NPH) insulin glargine is a new long-acting peakless analogue with lower incidence of nocturnal hypoglycemia having the potential to decrease the frequency of hypoglycemia of insulin therapy. Modern type 2 diabetes therapy guidelines recommend insulin for an increasing population of patients. There is no doubt that type 2 diabetic patients suffer from hypoglycemia under insulin therapy, however it is not clear whether the extensive studies on hypoglycemia in type 1 patients apply also for type 2 diabetes. Recent reports indicate that type 2 diabetic patients of long duration react similarly to a hypoglycemic clamp as type 1 diabetic patients while well controlled type 2 diabetics had even more favorable thresholds for counter-regulatory hormone secretion. On the basis of these considerations the aims of this study are to 1) more precisely define the mechanisms of hypoglycemia in type 2 diabetes, 2) to investigate differences on glucose and lactate metabolism of bedtime NPH insulin versus glargine. To address these objectives we will use the hypoglycemic clamping technique combined with infusion of stable isotopes of glucose and lactate and non-invasive measurement of muscle flow characteristics at hypoglycemia.

Eligibility criteria: Inclusion Criteria:

* Type 2 Diabetes mellitus
* Therapy may be with either insulin alone or in combination with oral anti-diabetic agents
* Metabolic control with HbA1c values \< 10%

Exclusion Criteria:

* Other than type 2 diabetes
* Pregnancy
* Systemic Corticosteroids, Beta-blockers
* Clinically relevant cardiovascular, gastrointestinal, hepatic, neurologic, endocrine, haematological or other major disease making implementation of the protocol or interpretation of the study results difficult
* History of drug or alcohol abuse
* Impaired renal function (serum creatinine \> 1.3 mg/dl)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: Clinical Research Unit
Study officials:
affiliation: Justus Liebig University
name: Thomas Linn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, Vahatalo M, Virtamo H, Nikkila K, Tulokas T, Hulme S, Hardy K, McNulty S, Hanninen J, Levanen H, Lahdenpera S, Lehtonen R, Ryysy L. Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia. 2006 Mar;49(3):442-51. doi: 10.1007/s00125-005-0132-0. Epub 2006 Feb 3.