title: Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients.
abstract: The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period. In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated. At the two different daily doses fasting plasma metformin concentrations were similar (3.23 +/- 0.35 mumol/l and 3.86 +/- 0.72 mumol/l, mean values +/- SEM, at low and high dose respectively). Drug peak values and averaged concentrations (4.66 +/- 0.39 mumol/l vs 6.35 +/- 0.69 mumol/l) were significantly higher when more drug was administered. Mean plasma glucose was lower when 1,700 mg/day instead of 1,000 mg/day of metformin was given (7.3 +/- 0.4 mmol/l vs 9.1 +/- 0.9 mmol/l, p less than 0.05). After dosing, at higher plasma metformin concentrations corresponded lower plasma glucose values. The averaged blood lactate levels resulted 1.46 +/- 0.4 mmol/l (p less than 0.05 vs matched diet treated diabetic patients) at the higher drug dose. A significant positive correlation emerged between mean plasma metformin concentrations and mean blood lactate levels (r: 0.76, p less than 0.02). Alanine, glycerol and B-OH-butyrate levels were similar at the two metformin daily doses, and were not correlated to plasma metformin. The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.
authors.affiliation: Istituto di Clinica Medica Generale e Terapia Medica II, University of Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Marchetti
authors.forename: F
authors.initials: F
authors.lastname: Gregorio
authors.forename: L
authors.initials: L
authors.lastname: Benzi
authors.forename: R
authors.initials: R
authors.lastname: Giannarelli
authors.forename: P
authors.initials: P
authors.lastname: Cecchetti
authors.forename: G
authors.initials: G
authors.lastname: Villani
authors.forename: G
authors.initials: G
authors.lastname: Di Cianni
authors.forename: A
authors.initials: A
authors.lastname: Di Carlo
authors.forename: P
authors.initials: P
authors.lastname: Brunetti
authors.forename: R
authors.initials: R
authors.lastname: Navalesi
mesh_terms: D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002087:Butyrates / Q000097:blood; D020148:Butyric Acid; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005990:Glycerol / Q000097:blood; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008687:Metformin / Q000097:blood* / Q000627:therapeutic use; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid
chemical_list: D001786:Blood Glucose; D002087:Butyrates; D007773:Lactates; D011773:Pyruvates; D020148:Butyric Acid; D019344:Lactic Acid; D019289:Pyruvic Acid; D008687:Metformin; D000409:Alanine; D005990:Glycerol