Serum Uric Acid And Major Diabetes Complications In Type 2 Diabetes Mellitus

Objective:The prevalence of type 2 diabetes mellitus(T2DM)has been increasing in China and more and more patients with T2 DM have developed diabetes complications.T2 DM itself and its complications seriously damage quality of life of these patients and shortened their life expectancy.With the change of diet,the prevalence of hyperuricemia in China has been increasing,too,with a trend of onset at young age.T2 DM is chracterized by insulin resistance,hyperglycemia,hypertension and abnormal lipid profile.As a common outcome of adequate lifestyle,hyperuricemia often appears in cluster with typical metabolic change in T2 DM.It is well established that hyperglycemia,hypertension and abnormal lipid profile are associated with diabetes complications.On the other hand,independent associations of serum uric acid(SUA)with diabetes complications and its interactive effects with other risk factors for these complications are yet to be investigated.This study focused on risk associations between SUA and macro-and microvascular complications with special attention to non-linear associations and additive interactions between two risk factors for increased risk of these complications in Chinese patients with T2 DM.Methods : From May 2013 to August 2013,a survey was conducted by Chinese Hospital Association in patients with T2 DM from top tertiary hospitals in China to learn the profile of management of patients with T2 DM.A total of 6800 inpatients with diabetes in 81 top tertiary care hospitals in 27 cities from 21 Chinese provinces were invited and agreed to participate in the survey and 6713 valid patients were analyzed in the present study.The major diabetes complications used in this analysis were acute complication(hypoglecemia),choronic cardiovascular disease(CVD)and microvascular disease(MVD).Self-reported asymptotic hypoglycaemia with plasma glucose ?3.9 mmol/L,hypoglycaemia episodes with symptoms in 1 month or hypoglycaemia that needed assistance from other people in 3 months before hospitalization was used to define hypoglycaemia.CVD was defined as having either prior coronary heart disease(CHD)or stroke or peripheral arterial disease(PAD).MVD was defined as diabetes retinopathya(DR)and diabetes nephropathy(DN).The restricted cubic spline analysis was used to capture the non-linear relationship patterns between SUA and complications of diabetes.Binary logistic regression was used to estimate odds ratios(OR)and 95% confidential interval(CI)of SUA for the clinical outcomes of interest.Additive interaction was qualitatively and quantitatively estimated by two measures,i.e.,relative excess risk due to interaction(RERI)and attributable proportion due to interaction(AP).In this study,significant RERI>0 and AP>0 indicates significant additive interaction.Results:Mean age of inpatients was 56.38(standard deviation: 10.55)years with a median of 3.00(interquartile: 0.41 to 6.05)years of duration of diabetes.Female patients accounted for 43.44%.Among 6713 patients with type 2 diabetes,409(6.09%)reported to have hypoglycaem(asymptomatic hypoglycemia: 25(0.37%),mild hypoglycaemia: 304(4.53%),severe hypoglycaemia: 80(1.19%));561(8.36%)suffered from CVD(CHD: 357 or 5.32%;stroke: 106 or 1.58%;PAD: 216 or 3.21%).408(6.08%)reported to have MVD(DN: 220(3.28%);DR:281(4.19%)).The associations of SUA and individual clinical outcomes are set out as below:1.SUA level was associated with hypoglycemia in patients with T2 DM,in non-linear manner.In multi-factor model,high SUA(?283 ?mol/L)increased the risk of hypoglycemia(OR: 1.98,95%CI: 1.58-2.48).The co-presence of mildly increased SUA(?283 ?mol/L)and mildly decreased esitimaed glomerular giltration rate(e GFR)(60<e GFR? 90 m L/min/1.73 m2)had an additive interactive effect towards increasing the risk of hypoglycaemia(Multivariable model: RERI: 2.11,95%CI:0.42-3.81;AP: 0.54,95%CI: 0.25-0.82).2.SUA levels were associated with CVD in T2 DM patients,in a roughly linear manner,and per 1 ?mol/L increase in SUA level was associated with a 0.1%increased risk of CVD.In multivariable analyses,high SUA(?283 ?mol/L)was associated with increased risk of CVD(OR of high versus low SUA: 1.49,95%CI:1.25-1.78).The co-presence of mildly increased SUA(?283 ?mol/L)and mildly decreased e GFR(60<e GFR?90 m L/min/1.73 m2)had an additive interactive effect towards increasing the risk of CVD(Multivariable RERI: 1.15,95%CI: 0.05-2.26;Multivariable AP: 0.48,95%CI: 0.15-0.81).The co-presence of mildly increased SUA and mildly decreased total bilirubin(TBIL)(<11.5 ?mol/L)had an additive interactive effect towards increasing the risk of CVD(Multivariable RERI: 4.40,95%CI: 3.25-5.54;Multivariable AP: 0.84,95%CI: 0.77-0.90).3.SUA levels were associated with MVD in a non-linear manner in T2 DM patients.In multivariable analyses,high SUA(?283 ?mol/L))was associated with increased risk of MVD(OR: 1.35,95%CI: 1.04-1.75).The co-presence of mildly increased SUA(?283 ?mol/L)and mildly decreased e GFR(60<e GFR?90 m L/min/1.73 m2)had an additive interactive effect towards increasing the risk of MVD(Multivariable RERI: 0.87,95%CI: 0.10-1.65;Multivariable AP: 0.66,95%CI: 0.32-0.99).The co-presence of mildly increased SUA and mildly decreased TBIL(<11.5 ?mol/L)had an additive interactive effect towards increasing the risk of MVD(Multivariable model: RERI: 1.06,95%CI: 0.40-1.73;AP: 0.58,95%CI: 0.32-0.84).Conclusions: SUA was associated with different diabetes complications in different manners in T2 DM.SUA was associated with hypoglycemia and MVD in non-linear manners in T2 DM.On the other hand,it was associated with CVD was in a roughly linear manner.In addition,mildly increased SUA level and mildly decreased e GFR had an additive interactive effect on the risk of the major complications of diabetes,i.e.,hypoglycemia,CVD and MVD.Mildly increased SUA level and mildly decreased TBIL level had an additive interactive effect on the risk of both CVD and MVD.The result in the present study need be confirmed in other populations in future studies,especially the low risk patients with type 2 diabetes.The biological mechanisms underlying interplays among SUA and other risk factors for the diabetes complications need to be investigated in further mechnistic studies.It is also warranted to test the potential usefulness of these novel risk factors for inclusion in existing CVD and MVD predicting tools in patients with type 2 diabetes.