Background/Purpose

Substantial evidence links gout and hyperuricemia to diabetes. Previous studies report an association between increasing uric acid (UA) levels, insulin resistance, and type 2 diabetes (T2DM).  Elevation in serum insulin is purported to increased serum UA levels through increased renal urate absorption.  This study sought to evaluate the effect of initiating insulin for T2DM on serum UA levels.

Methods

We conducted a retrospective analysis on patients with both T2DM and gout.  Patients were selected from a linked dataset from an electronic medical record (EMR) and Medicare claims data. This data set includes patients at one academic medical center with diagnoses of gout and hyperuricemia as confirmed in the EMR who also had T2DM (defined as hemoglobin A1c (HbA1c) > 6.5%, ICD-9-CM code 250.x or use of diabetic medications). An insulin-initiating cohort and a non insulin-initiating cohort were compared for changes in UA. Cohorts were matched on sex, age at first UA measurement, and length of time between UA measurements.  The first UA measurement occurred before insulin initiation and the second at least 3 months later; matched time points were used in the non-initiators.

Potential cofounders including HbA1c, creatinine, body mass index, length of time between UA measurements and medications (allopurinol, hydrochlorothiazide, losartan, tacrolimus, cyclosporine) were adjusted for in a series of linear regression models. 

Results

23 patients met criteria for insulin initiation and 23 were matched non-insulin initiators. Mean age was 59 and 57 years for the insulin and non-insulin cohorts, respectively, both cohorts were 52% female. Patients initiating insulin had a larger increase in mean UA levels, 6.41mg/dl to 7.66mg/dl  (mean change 1.25 mg/dl, interquartile range, IQR: -0.7,2.3) compared to non-insulin initiators, mean increase from 6.17mg/dl to 6.23mg/dl (mean change 0.06 mg/dl, IQR: -1.1,0.9 p = 0.06). Of the covariates, only length of time between UA measurements had an unadjusted p-value < 0.05 and was advanced to the final adjusted model.  The final linear regression showed that insulin use was associated with a 1.25mg/dl greater increase in UA levels when compared to non-insulin initiators  (p value = 0.02).  Adjusting for allopurinol did not attenuate results.  (Table)

Conclusion

Insulin initiation in patients with T2DM was associated with a statistically significant increase in serum UA levels. This may have clinical implications, including risk of gout flares.  Gout attack prophylaxis might be useful in the setting of insulin initiation among patients with gout. A prospectively designed study would help overcome potential limitations of our retrospective design.

Table 1. Regression analysis of covariate effects on change in uric acid in insulin initiators
Model		β	95% CI	P
A	Crude Model: Insulin + UA1	1.29	0.15, 2.44	0.03
B	Model A + age + months between UA1 & UA2	1.25	0.16, 2.34	0.03
C	Model B + hemoglobin A1c	1.47	-0.06, 3.00	0.06
D	Model C + creatinine + body mass index	1.33	-0.28, 2.94	0.10
E	Insulin+UA1+months between UA1 & UA2	1.25	0.18, 2.33	0.02
Addition of relevant medications		β	95% CI	P
F	Model D + Allopurinol	1.36	-0.12, 2.84	0.07
G	Model D  + Hydrochlorothiazide	1.41	-0.17, 2.99	0.08
H	Model D + Losartan	1.45	-0.07, 2.96	0.06
I	Model D + Tacrolimus	1.48	-0.04, 3.00	0.06
J	Model D + Cyclosporine	1.61	0.03, 3.20	0.05

β= beta co-efficient from linear regression model, represents the change in uric acid among insulin initiators compared to matched non-initiators; 95% CI=95% confidence interval; UA1=1^st uric acid measurement; UA2= 2^nd uric acid measurement

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-initiating-pharmacologic-insulin-on-serum-uric-acid-levels-in-patients-with-diabetes/