200,000 people study data: Is lower creatinine really better?

Skeletal muscle is a major target tissue for peripheral insulin resistance (IR)
.
Therefore, the loss of muscle may lead to the reduction of insulin targets and the production of IR
.
Increased IR associated with low muscle mass may predispose to the development of diabetes
.
According to the National Health and Nutrition Examination Survey III data, decreased muscle mass in subjects 20 years or older was associated with increased IR
.
In turn, greater thigh muscle mass was associated with a lower risk of type 2 diabetes (T2DM) events among thin Japanese Americans without diabetes
.
According to the Korean National Health and Nutrition Examination Survey, in Korean subjects ≥20 years old, decreased skeletal muscle mass is associated with increased IR and is a risk factor for diabetes in non-obese people
.
A prospective study including middle-aged and older Korean adults without diabetes showed that, for a given body mass index (BMI) category, decreased muscle mass was associated with an increased risk of T2DM
.

Serum creatinine is primarily a breakdown product of creatine, depends on total skeletal muscle mass, and is continuously eliminated at steady state
.
Although serum creatinine is known to be affected by age, gender, ethnicity, and dietary protein intake, serum creatinine is very stable and is often used as a surrogate measure of skeletal muscle mass when protein intake is adequate
.
Therefore, low serum creatinine may be associated with the development of T2DM
.
Because measuring serum creatinine levels is cheaper and easier than measuring skeletal muscle mass, evaluating the relationship between serum creatinine levels and the incidence of T2DM is of interest for early detection of high-risk T2DM
.

Some studies suggest that low serum creatinine levels are associated with an increased risk of diabetes
.
However, it is difficult to generalize because previous studies were conducted in a single center with a small number of participants
.
This study aimed to evaluate the association between serum creatinine levels and the risk of T2DM events in the Korean population over the age of 40 using a large cohort database based on Korea's National Health Insurance Service (NHIS) data from 2009 to 2015
.

We analyzed 264,832 nondiabetic adults aged 40 and older who had undergone at least one national health checkup in the National Health Insurance Service cohort of Korea between 2009 and 2015
.
Hazard ratios for T2DM were calculated
.

Finally, a total of 139,109 men and 125,723 women were included in the study
.
During follow-up, 32,209 men and 32,965 women were diagnosed with T2DM
.
Table 1 shows baseline characteristics of men by baseline serum creatinine category
.
Men with elevated serum creatinine levels tended to have elevated mean BMI, DBP, and fasting plasma glucose
.
In men, serum creatinine levels were inversely associated with the risk of T2DM in a J-shape, with men with serum creatinine between 0.
90 and 1.
19 mg/dl having the lowest risk (Figure 1)
.
This inverse J-shaped association between serum creatinine levels and T2DM risk persisted after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose
.
Men with the lowest serum creatinine had the highest risk of developing T2DM
.
The HR of diabetes incidence by creatinine level in men is shown in Table 2
.
According to serum creatinine category, the hazard ratios for T2DM development were 1.
00 (reference), 0.
90 (0.
7–0.
89 mg/dl), 0.
88 (0.
9–1.
19 mg/dl) and 0.
95 (≥1.
2 mg/dl)
.

Table 3 shows baseline characteristics of women according to baseline serum creatinine category
.
Women with elevated serum creatinine levels tended to have elevated mean BMI, DBP, and fasting plasma glucose
.
Among women, patients with serum creatinine levels below 1.
1 mg/dl tended to have an increased risk of T2DM, although the association was not yet statistically significant (Figure 2)
.
Women with the highest serum creatinine levels had the highest risk of developing T2DM
.
However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose
.
The HR of diabetes incidence by creatinine level in women is shown in Table 4
.
According to serum creatinine category, the hazard ratios for developing T2DM in women were 1.
00 (reference), 0.
99 (0.
6-0.
79 mg/dl), 0.
98 (0.
8-1.
09 mg/dl) and 1.
06 (≥1.
1 mg/dl)
.

Overall, in men, decreased serum creatinine levels were significantly associated with increased risk of T2DM in men with creatinine levels below 1.
20 mg/dl, and serum creatinine levels had an inverse J-shaped association with T2DM risk
.
This association persisted after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose
.
Among women, there was a trend that serum creatinine levels were inversely related to T2DM risk in patients with serum creatinine below 1.
1 mg/dl
.
However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose
.
Therefore, measurement of serum creatinine is useful for screening people at high risk of diabetes, especially men
.
Furthermore, these findings will contribute to understanding the heterogeneous pathophysiology of T2DM
.

Original source:

Do Kyeong Song , et al.
Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study
.