Circ J. 2015;79(1):210-5. doi: 10.1253/circj.CJ-14-0689.

Elevated fasting insulin level significantly increases the risk of microalbuminuria.

 

Ryoo JH, Park SK, Jung JY.

Department of Preventive Medicine, School of Medicine, Kyung Hee University.

 

Abstract

BACKGROUND: Microalbuminuria is significantly associated with long-term prognosis in the general population as well as in diabetic patients. It is well known that insulin resistance (IR) can induce microalbuminuria, but an elevated fasting insulin level, which is an early clinical manifestation of IR, as a risk factor for microalbuminuria has not been clarified, so we investigated the association between fasting insulin level and the development of microalbuminuria in a general population.

METHODS AND RESULTS: A total of 1,192 non-diabetic Korean men without microalbuminuria in 2005 were followed until 2010. They were categorized into 3 groups according to their fasting insulin levels and monitored for the development of microalbuminuria. The incidence of microalbuminuria was compared among groups, and Cox proportional hazards models were used to calculate the hazard ratios for microalbuminuria according to the fasting insulin levels. During 4,013.0 person-years of follow-up, 51 incident cases of microalbuminuria developed between 2006 and 2010. The incidence of microalbuminuria increased in proportion to the fasting insulin levels (tertile 1: 1.8%, tertile 2: 4.5%, tertile 3: 6.5%, P<0.001). Hazard ratios for microalbuminuria also increased in proportion to the fasting insulin levels [tertile 1: reference, tertile 2: 2.44 (1.01-5.89), tertile 3: 3.30 (1.40-7.78), respectively, P for trend 0.013].

CONCLUSIONS: Elevated fasting insulin level was associated with the future development of microalbuminuria.

PMID: 25391257

 

Supplements:

Microalbuminuria, defined as a urine albumin creatinine ratio (UACR) of 30 – 299 mg/g, has important clinical implication. It is well known that the presence of microalbuminuria is an early predictor of poor renal outcomes and cardiovascular events in diabetic patients. Additionally, recent studies have been reported that microalbuminuria is significantly associated with cardiovascular morbidity and mortality even in non-diabetic general population.

Nonetheless, the predisposing factor to microalbuminuria is not well established in non-diabetic general population. Such uncertainty would raise some questions. Which person is more predisposed to microalbuminuria than others? What are the potential risk factor for microalbuminruia in non-diabetic general population? These question currently remain controversial.

​ We had a notion that microalbuminuria is closed linked to insulin resistance. The development and progression of microalbuminuria is deeply associated with insulin resistance, which hazardous milieu affecting the development of other metabolic disease such as type 2 diabetes, impaired glucose tolerance, metabolic syndrome. Especially, insulin metabolism related to insulin resistnace plays a pivotal role in the pathogenesis of aforementioned diseases. Therefore, it is probable hypothesis that insulin resistance precedes the developement of microabluminuria and confers the potential susceptibility for microalbuminuria even in non-diabetic general population. If so, the insulin resistance or insulin itself can be a tool to predict the occurrence of microalbuminuria in non-diabetic population.

So for, several studies have demontrated that hypersinulinemia is associated with the development of the microalbuminuria. However, to the best of our knowledge, there was no prospective cohort study with large scale actually showing the predictability of elevated fasting insulin level in microalbuminuria. Especially, we stratified the baseline fasting insulin level, which enabled us to evaluate the incidental risk of microalbuminuria according to the fasting insulin level in general population.

In this prospective cohort study, a total of 3,454 men(30-59 years old) had examined the urine albumin creatinine ratio(UACR) in 2005, and 1,192 participant were enrolled final analysis. The total follow-up period was 4,013.0 person year and average follow-up period was 3.37 person years. The starting point in the study, all participants didn’t have diabetes or microalbuminuria. They were divided into four groups according to the fasting plasma insulin level.

At the end of study, the risk of microalbuminuria showed a clear dose-response relationship with fasting hypersinsulinemia. People with high fasting insulin level had a higher risk of microalbuminuria. Our study results showed a very convincing evidence that fasting hyperinsulinemia is a good predictor of future microalbuminuria in non-diabetic population.

Fasting insulin can be easily measured with a simple blood test. We hope that doctors can be easily find a risk group of microalbuminuria even in primary medical institutions. However, further researches are needed in order to determine the fasting insulin is a useful tool in clinical practice.

One more interesting thing is the fasting plasma insulin might be able to predict other diseases. In our previous study, the incidence of hypertension in non-diabetic population increased according to the baseline fasting insulin level (first quartile: 13.3%, second quartile: 15.4%, third quartile: 17.5%, fourth quartile: 23.2%, P<0.001). (1) Of course, insulin resistance is highly likely to be underlying reason.

Our next goal is to determine whether the fasting insulin level is a useful predictive tool of other disease – such as metabolic disease – in general population. Additionally, as we are well aware of our study limitation that study population consists of only Korean men, we will verify this hypothesis in more diverse population. We can say that the study is only just beginning.

We are sure that the Kangbuk Samsung Cohort Sudy (KSCS) data can be solution of such our mission. This cohort study participants consisted of healthy Korean men undergoing a medical health check-up program at the Health Promotion Center of Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea.

KSCS is collecting and adjusting the data of health check-up program that has been provided to Korean men in The Total healthcare center of Kangbuk Samsung Hospital affiliated to Sungkyunkwan University, School of Medicine.

The Total healthcare center of Kangbuk Samsung Hospital we are working is one of the biggest healthcare center in Korea providing general population with medical health check-up regularly. Korea’s Industrial Safety and Health law regulates that all of Korean employee should get regular medical health check-up supported by their company, and our center is providing medical health check-up to about 120,000 employees. Thus, such excellent system of our country and center gave us the precious opportunity to conduct this study. Therefore, we are deeply appreciating to staffs working in Kangbuk Samsung Hospital. Especially, we would like to express the greatest thanks to staffs of Kangbuk Samsung Cohort Study (KSCS). That’s because their contribution and effort to research makes it possible for the member of Kangbuk Samsung Hospital to conduct study.

 

Reference

  1. Park SK, Jung JY, Choi WJ, Kim YH, Kim HS, Ham WT, Shin H, Ryoo JH. Elevated fasting serum insulin level predicts future development of hypertension. Int J Cardiol. 2014 Mar 15;172(2):450-5. doi: 10.1016/j.ijcard.2014.01.087. Epub 2014 Jan 25.

 

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