Steroids decrease insulin sensitivity in RA patients

[Guest guest]

Rheumawire

May 25, 2004

Steroids decrease insulin sensitivity in RA patients

Johannesburg, South Africa - Rheumatoid arthritis (RA) patients who have

taken either oral prednisone or high doses of pulsed glucocorticoids are

likely to have decreased insulin sensitivity, Dr H Dessein

(Johannesburg Hospital and Milpark Hospital, South Africa) reports in

the May 2004 issue of the Journal of Rheumatology [1].

" Since decreased insulin sensitivity is an independent risk factor for

cardiovascular (CV) disease, glucocorticoids may contribute to the

excess CV-event rates in RA, " Dessein writes.

Dessein and colleagues at Johannesburg Hospital and the University of

Witwatersrand Centre for Diabetes and Endocrinology followed 92

consecutive RA patients for at least 6 months. Patients taking

lipid-lowering or antidiabetic drugs were excluded. The majority of the

group (90%) were women, mean age was 56, mean disease duration was 11

years, and mean follow-up duration at this clinic was 6 years. Of the

patients, 79% were positive for rheumatoid factor (RF).

More than half of the patients had high body mass index (BMI),

hypertension, dyslipidemia, or more than 1 of these. Of the patients, 72

(78%) had decreased insulin sensitivity and 12 had type 2 diabetes.

The researchers measured insulin sensitivity by the Quantitative Insulin

Sensitivity Check Index (QUICKI). QUICKI values in study subjects were

compared with normal values obtained in 94 healthy adults, for whom the

median QUICKI was 0.400. Decreased insulin sensitivity was defined as

values below the lower 95% confidence interval in the normal subjects

(0.393).

The researchers examined glucocorticoid-therapy variables, including

current prednisone exposure; current prednisone dose; previous exposure

to prednisone; previous exposure to pharmacological doses of prednisone

(>4 mg per day); duration of pharmacological doses of prednisone; total

number, mean yearly frequency, and mean dose of pulses used; and

cumulative oral, pulsed, and total glucocorticoid quantities.

Of the patients, 40% had received oral prednisone (duration 1 month to

20 years) and 20% were on prednisone at the time of completion of the

study. All patients had received some type of pulsed methylprednisolone.

At completion of the study, 91% of patients were on some type of DMARD,

most commonly methotrexate (77/94).

" Ever having taken prednisone and high yearly frequencies of pulsed

glucocorticoid administrations were significantly associated with

decreased insulin sensitivity, " Dessein reports. Mean QUICKI was 0.348

in patients who had ever taken prednisone vs 0.366 in those who had

never taken prednisone (p<0.01). Mean fasting insulin concentrations

were 8.6 in patients who had never taken prednisone vs 12.4 in those who

had taken prednisone (p=0.026). Mean fasting insulin level in control

subjects was 4.6 (range 4.2-5.0).

The BMI was higher in patients with decreased insulin sensitivity, and

Dessein notes that " overall, patients with normal insulin sensitivity

had a normal BMI while those with reduced insulin sensitivity had an

elevated BMI. "

However, multiple regression analyses showed that having taken

prednisone and having taken high mean pulsed glucocorticoid doses

predicted reduced insulin sensitivity independently of BMI and other

characteristics. None of the other glucocorticoid-therapy

characteristics were independently associated with insulin sensitivity.

Dessein notes from a previous study that an 18% increase in fasting

insulin concentration was reported as being independently associated

with a 1.7-fold increased risk for ischemic heart disease [2].

" Our finding that the mean fasting insulin concentrations were 2.2-fold

higher in RA patients than in controls suggests a potential role for

reduced insulin sensitivity in CV disease in RA. Insulin sensitivity was

significantly more reduced in patients who had received oral

glucocorticoids compared with those who had not been exposed to such

therapy, " Dessein said.

This effect is reportedly irreversible in about 50% of patients despite

glucocorticoid dose reductions or drug withdrawal. Dessein suggests that

the decrease in insulin sensitivity might be prevented if a

thiazolidinedione such as troglitazone were given at the same time as

the glucocorticoid. He also proposes additional research on the role of

preventive measures such as vitamin C, antioxidants, dietary

intervention, and exercise to enhance insulin sensitivity in RA patients

treated with glucocorticoids.

Janis

Sources

1. Dessein PH, Joffe BI, Stanwix AE, Christian BF, Veller M.

Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J

Rheumatol 2004 May; 31(5):867-74.

2. Despres JP, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an

independent risk factor for ischemic heart disease. N Engl J Med 1996

Apr 11; 334(15):952-7.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[Guest guest]

This is a very interesting study . It would be nice to know that

increased CV disease is a result of steroids rather than the RA disease

itself.

a

> Rheumawire

> May 25, 2004

>

> Steroids decrease insulin sensitivity in RA patients

>

> Johannesburg, South Africa - Rheumatoid arthritis (RA) patients who have

> taken either oral prednisone or high doses of pulsed glucocorticoids are

> likely to have decreased insulin sensitivity, Dr H Dessein

> (Johannesburg Hospital and Milpark Hospital, South Africa) reports in

> the May 2004 issue of the Journal of Rheumatology [1].

>

> " Since decreased insulin sensitivity is an independent risk factor for

> cardiovascular (CV) disease, glucocorticoids may contribute to the

> excess CV-event rates in RA, " Dessein writes.

>

> Dessein and colleagues at Johannesburg Hospital and the University of

> Witwatersrand Centre for Diabetes and Endocrinology followed 92

> consecutive RA patients for at least 6 months. Patients taking

> lipid-lowering or antidiabetic drugs were excluded. The majority of the

> group (90%) were women, mean age was 56, mean disease duration was 11

> years, and mean follow-up duration at this clinic was 6 years. Of the

> patients, 79% were positive for rheumatoid factor (RF).

>

> More than half of the patients had high body mass index (BMI),

> hypertension, dyslipidemia, or more than 1 of these. Of the patients, 72

> (78%) had decreased insulin sensitivity and 12 had type 2 diabetes.

>

> The researchers measured insulin sensitivity by the Quantitative Insulin

> Sensitivity Check Index (QUICKI). QUICKI values in study subjects were

> compared with normal values obtained in 94 healthy adults, for whom the

> median QUICKI was 0.400. Decreased insulin sensitivity was defined as

> values below the lower 95% confidence interval in the normal subjects

> (0.393).

>

> The researchers examined glucocorticoid-therapy variables, including

> current prednisone exposure; current prednisone dose; previous exposure

> to prednisone; previous exposure to pharmacological doses of prednisone

> (>4 mg per day); duration of pharmacological doses of prednisone; total

> number, mean yearly frequency, and mean dose of pulses used; and

> cumulative oral, pulsed, and total glucocorticoid quantities.

>

> Of the patients, 40% had received oral prednisone (duration 1 month to

> 20 years) and 20% were on prednisone at the time of completion of the

> study. All patients had received some type of pulsed methylprednisolone.

> At completion of the study, 91% of patients were on some type of DMARD,

> most commonly methotrexate (77/94).

>

> " Ever having taken prednisone and high yearly frequencies of pulsed

> glucocorticoid administrations were significantly associated with

> decreased insulin sensitivity, " Dessein reports. Mean QUICKI was 0.348

> in patients who had ever taken prednisone vs 0.366 in those who had

> never taken prednisone (p<0.01). Mean fasting insulin concentrations

> were 8.6 in patients who had never taken prednisone vs 12.4 in those who

> had taken prednisone (p=0.026). Mean fasting insulin level in control

> subjects was 4.6 (range 4.2-5.0).

>

> The BMI was higher in patients with decreased insulin sensitivity, and

> Dessein notes that " overall, patients with normal insulin sensitivity

> had a normal BMI while those with reduced insulin sensitivity had an

> elevated BMI. "

>

> However, multiple regression analyses showed that having taken

> prednisone and having taken high mean pulsed glucocorticoid doses

> predicted reduced insulin sensitivity independently of BMI and other

> characteristics. None of the other glucocorticoid-therapy

> characteristics were independently associated with insulin sensitivity.

>

> Dessein notes from a previous study that an 18% increase in fasting

> insulin concentration was reported as being independently associated

> with a 1.7-fold increased risk for ischemic heart disease [2].

>

> " Our finding that the mean fasting insulin concentrations were 2.2-fold

> higher in RA patients than in controls suggests a potential role for

> reduced insulin sensitivity in CV disease in RA. Insulin sensitivity was

> significantly more reduced in patients who had received oral

> glucocorticoids compared with those who had not been exposed to such

> therapy, " Dessein said.

>

> This effect is reportedly irreversible in about 50% of patients despite

> glucocorticoid dose reductions or drug withdrawal. Dessein suggests that

> the decrease in insulin sensitivity might be prevented if a

> thiazolidinedione such as troglitazone were given at the same time as

> the glucocorticoid. He also proposes additional research on the role of

> preventive measures such as vitamin C, antioxidants, dietary

> intervention, and exercise to enhance insulin sensitivity in RA patients

> treated with glucocorticoids.

>

> Janis

>

> Sources

>

> 1. Dessein PH, Joffe BI, Stanwix AE, Christian BF, Veller M.

> Glucocorticoids and insulin sensitivity in rheumatoid arthritis. J

> Rheumatol 2004 May; 31(5):867-74.

>

> 2. Despres JP, Lamarche B, Mauriege P, et al. Hyperinsulinemia as an

> independent risk factor for ischemic heart disease. N Engl J Med 1996

> Apr 11; 334(15):952-7.

>

>

>

>

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

>

>

>