Insulin-stimulated increase in serum leptin levels precedes and correlates with weight gain during insulin therapy in type 2 diabetes.
BACKGROUND
Infusion of insulin acutely stimulates leptin production and chronic insulin treatment is associated with elevated serum leptin levels and body weight in subjects with type 2 diabetes.


OBJECTIVE
The objective of the study was to investigate the relationship between insulin administration, leptin levels, and weight gain in subjects with type 2 diabetes.


METHODS
This was a post hoc analysis of two randomized, controlled trials.


METHODS
The study was conducted at an outpatient clinic.


METHODS
Subjects included 35 (study 1) and 32 (study 2) poorly controlled oral hypoglycemic agent (OHA)-treated type 2 diabetic subjects.


METHODS
Study 1: subjects were investigated during a hyperinsulinemic, euglycemic glucose clamp and 12 months after being randomly allocated to start insulin or continue on OHAs. Study 2: 1 yr treatment with either OHAs and lifestyle intervention or insulin with or without concomitant lifestyle intervention.


METHODS
Changes in serum leptin levels during clamp and during 1 yr of treatment in relationship to changes in body weight.


RESULTS
Study 1: during acute insulin infusion leptin levels increased by 10% (P < 0.001). During 1 yr of insulin therapy, mean body weight increased by 6%, whereas the fasting leptin levels increased by 108% (both P < 0.001). The weight gain observed at 1 yr correlated with the increase in leptin levels observed during the clamp (r = 0.62, P = 0.003). Study 2: mean body weight increased by 4% (P < 0.01), whereas leptin levels increased by 56% (P < 0.001) during 1 yr of insulin treatment and the increase in leptin preceded the increase in body weight.


CONCLUSIONS
Significant correlations were observed between insulin's effect on serum leptin levels and the increase in weight that accompanied insulin therapy.
Aas
Anne-Marie
AM
Department of Nutrition and Dietetics, Aker University Hospital, Trondheimsveien 235, Oslo, Norway. a.m.aas@medisin
Hanssen
Kristian F
KF
Berg
Jens Petter
JP
Thorsby
Per M
PM
Birkeland
Kåre I
KI
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D015430:Weight Gain
D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; C517652:hemoglobin A1c protein, human