GLUCOSAMINE ET DIABETE

GLUCOSAMINE ET DIABETE
QUESTION : Est-ce que la glucosamine est contre-indiquée chez les
diabétiques?
AUTEUR : Mélanie Lecault (FÉVRIER 2008)
P
:
population adulte souffrant d’arthrose et de diabète
I
:
glucosamine
C
:
placebo
O
:
contrôle de la glycémie
CONTEXTE : Question suscitée lors de la réalisation d’un PICO sur la
glucosamine et l’ostéoarthrite. J’avais aussi une notion lointaine que la
glucosamine était contre-indiquée chez les diabétiques à cause de l’effet sur la
glycémie.
RECHERCHE :
Cochrane : glucosamine AND diabetes (7 résultats; 0 pertinent)
DARE : glucosamine AND diabetes (0 résultat)
CRCT: glucosamine AND diabetes (45 résultats; 3 pertinents)
PubMed : glucosamine AND diabetes limité aux «clinical trials» et aux
«randomized controlled trials» (67 résultats; 4 pertinents dont 3 trouvés dans le
CRCT et une exclue car infusion de glucosamine
Trip Database : glucosamine (1 résultat, et deux liens pertinents)
RESULTATS :
1) Muniyappa R, Karne RJ, Hall G, Crandon SK, Bronstein JA, Ver MR, Hortin
GL, Quon MJ. Oral glucosamine for 6 weeks at standard doses does not
cause or worsen insulin resistance or endothelial dysfunction in lean or
obese subjects. Diabetes 2006; 55(11):3142-50.
Glucosamine is a popular nutritional supplement used to treat osteoarthritis.
Intravenous administration of glucosamine causes insulin resistance and
endothelial dysfunction. However, rigorous clinical studies evaluating the safety
of oral glucosamine with respect to metabolic and cardiovascular
pathophysiology are lacking. Therefore, we conducted a randomized, placebocontrolled, double-blind, crossover trial of oral glucosamine at standard doses
(500 mg p.o. t.i.d.) in lean (n = 20) and obese (n = 20) subjects. Glucosamine or
placebo treatment for 6 weeks was followed by a 1-week washout and crossover
to the other arm. At baseline, and after each treatment period, insulin sensitivity
was assessed by hyperinsulinemic-isoglycemic glucose clamp (SI(Clamp)) and
endothelial function evaluated by brachial artery blood flow (BAF; Doppler
ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound
with microbubble contrast) before and during steady-state hyperinsulinemia.
Plasma glucosamine pharmacokinetics after oral dosing were determined in each
subject using a high-performance liquid chromatography method. As expected, at
baseline, obese subjects had insulin resistance and endothelial dysfunction when
compared with lean subjects (SI(Clamp) [median {25th-75th percentile}] = 4.3
[2.9-5.3] vs. 7.3 [5.7-11.3], P < 0.0001; insulin-stimulated changes in BAF [%
over basal] = 12 [-6 to 84] vs. 39 [2-108], P < 0.04).
Leur conclusion: When compared with placebo, glucosamine did not cause
insulin resistance or endothelial dysfunction in lean subjects or significantly
worsen these findings in obese subjects. The half-life of plasma glucosamine
after oral dosing was approximately 150 min, with no significant changes in
steady-state glucosamine levels detectable after 6 weeks of therapy. We
conclude that oral glucosamine at standard doses for 6 weeks does not cause or
significantly worsen insulin resistance or endothelial dysfunction in lean or obese
subjects.
2) Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin
supplementation on glycosylated hemoglobin levels in patients with type 2
diabetes mellitus: a placebo-controlled, double-blinded, randomized
clinical trial. Archives of internal medicine 2003; 163(13): 1587-90.
BACKGROUND: With increasing use of glucosamine-containing supplements for
the treatment of osteoarthritis, there is increasing concern in the medical
community about possible toxic effects. The present study was undertaken to
determine whether glucosamine supplementation altered hemoglobin A1c
concentrations in patients with well-controlled diabetes mellitus. OBJECTIVE: To
evaluate possible effects of glucosamine supplementation on glycemic control in
a selected population of patients with type 2 diabetes mellitus. DESIGN:
Placebo-controlled, double-blinded, randomized clinical trial. SETTING:
Outpatient, diabetes monitoring clinic. PATIENTS: Patients were typically elderly
patients, evenly divided between men and women. Most of the patients were
being treated with 1 or 2 drugs for glycemic control. INTERVENTION: In daily
doses for 90 days, patients received either placebo or a combination of 1500 mg
of glucosamine hydrochloride with 1200 mg of chondroitin sulfate (Cosamin DS;
Nutramax Laboratories Inc, Edgewood, Md).Main Outcome Measure Hemoglobin
A1c levels before and after 90 days of therapy. RESULTS: There were 4
withdrawals from the glucosamine-treated group. Three were related to
comorbidities (myocardial infarction, congestive heart failure, and atrial
fibrillation) and 1 to a possible adverse reaction (excessive flatus). No other
patient reported any adverse effects of glucosamine therapy, and no patient had
any change in their diabetes management. Mean hemoglobin A1c concentrations
were not significantly different between groups prior to glucosamine therapy.
Posttreatment hemoglobin A1c concentrations were not significantly different
between groups, nor were there any significant differences within groups before
and after treatment. CONCLUSION: This study demonstrates that oral
glucosamine supplementation does not result in clinically significant alterations in
glucose metabolism in patients with type 2 diabetes mellitus.
CONCLUSION:
La glucosamine en hautes doses par voie intraveineuse (Monauni et al 2000)
cause une augmentation de la résistance à l’insuline chez les animaux et les
humains en interférant avec la régulation du transport du glucose.
L’étude de Muniyappa et al n’a pas montré de détérioration de la résistance à
l’insuline chez des sujets non-diabétiques. Malgré qu’il s’agit d’une étude bien
conçue, les sujets diabétiques étaient exclus, et la durée ne nous permet pas de
conclure à l’innocuité de la glucosamine, puisque les patients l’utilisent en
général pour plus de six semaines.
L’étude de Scroggie et al impliquait des patients dont le diabète était bien
contrôlé et stable. L’étude était très petite (n=22 et n=12). La maladie semblait
légèrement moins sévère dans le groupe placebo puisque ce groupe prenait
moins d’hypoglycémiants oraux, mais les valeurs d’HbA1c étaient semblables.
L’étude était courte encore une fois (trois mois) et ne permet pas de se
prononcer sur l’utilisation de la glucosamine à long terme.
Une autre étude (Albert et al 2007) encore plus courte (deux semaines) et très
petite (n=12) n’ont pas démontré d’effet délétère de la glucosamine chez les
diabétiques.
Donc, les études ayant examiné l’effet de la glucosamine orale sur le contrôle
glycémique, chez les patients diabétiques ou non, n’ont pas démontré d’effet
néfaste. Cependant, les études sont peu nombreuses et très courtes. Nous ne
pouvons donc pas nous prononcer sur l’effet de la glucosamine à long terme.
Des opinions d’experts (Marshall et al 2006; Trip Database) affirment qu’aucune
donnée ne porte à croire que l’effet à long terme serait différent de l’effet observé
à court terme chez les diabétiques. On recommande quand même une
surveillance plus étroite de la glycémie lors de l’introduction de la glucosamine. Il
faut toutefois être prudent chez les non-diabétiques car il serait possible que la
glucosamine aggrave l’intolérance au glucose chez des patients nondiagnostiqués (Biggee et al).
Autres références non citées en entier ci-haut:
Albert SG et al. The effect of glucosamine on serum HDL cholesterol and
apolipoprotein A1 levels in people with diabetes. Diabetes Care 2007;
30(11): 2800-3.
Biggee BA et al. Effects of oral glucosamine sulphate on serum glucose and
insulin during an oral glucose tolerance test of subjects with osteoarthritis.
Annals of Rheumatic Diseases 2007: 66: 260-2.
Marshall PD,Tweed EM. Do glucosamine and chondroitin worsen blood
sugar control in diabetes? The Journal of Family Practice 2006;55 (12):1091-3.
Monauni T et al. Effects of glucosamine infusion on insulin secretion and
insulin action in humans. Diabetes 2000; 49: 926-35.
Trip Database: Can glucosamine worsen control in type 2 diabetes?
[http://www.clinicalanswers.nhs.uk/index.cfm?question=7494]. Date de parution:
6 février 2008. Consulté : 23 février 2008.
Question: Can glucosamine worsen control in type 2 diabetes?
Answer:In 2002 UK Medicine Information, as part of their FAQ series, answered the question “Is
it safe for people with diabetes to take glucosamine?”. We recommend you read the full article,
although the summary paragraph states:“Whilst further long-term safety studies are needed for
glucosamine, existing data does not indicate that oral administration adversely affects
hyperglycaemic control in diabetes. Nevertheless, it would be prudent to monitor the diabetic
patient for altered response if they start taking glucosamine.”
A 2005 article ‘An Evidence-based Systemic Review of Glucosamine Conducted by the Natural
Standard Research Collaboration’ [2], this reports: “… The effect of glucosamine on glucose
levels or insulin resistance has been controversial, and it remains unclear if interactions with
agents possessing glycemic properties may occur. Despite initial concerns about use in diabetic
patients based largely on in vitro and rat studies noting insulin resistance and possible glycemic
effects and preliminary human work, more recent human research reports no significant effects
(including on hemoglobin A1c levels in patients with type 2 diabetes after 90 days of therapy).
Clinically relevant effects on blood sugars have not been noted in several clinical trials.”
A 2006 UK Medicines Information article ‘Glucosamine – what are the adverse effects?’ [3],
includes the following:“Glucosamine does not appear to adversely affect plasma blood glucose in
patients without diabetes. However, data relating to its effects in patients with diabetes are
lacking. It may be wise for patients with diabetes to monitor their blood glucose levels more
closely if they start to take glucosamine, increase their dose or change the product taken.”
Finally, also in 2006, the American Family Physicians Inquiries Network reported [4]:“Despite
theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin
(1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose
diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A,
consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that
glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose
intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence).
Long-term effects are unknown; however, no compelling theoretical or incidental data suggest
that long-term results should be different (SOR: C, expert opinion). Further studies are required to
clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose
intolerance.”