Simple Muscle Marker May Predict Return to Normal Blood Sugar, Study Finds

For the millions of people worldwide who are told each year that their fasting blood sugar has crept into the danger zone, one of the most hopeful messages in metabolic research is that the diagnosis is not a one-way street. Impaired fasting glucose, the gray zone between normal metabolism and full-blown diabetes, can and often does revert to healthy normoglycemia. The question that has long frustrated clinicians is which patients will make that journey back and which will slide onward toward type 2 diabetes. A new analysis published in BMC Endocrine Disorders suggests that part of the answer may lie in an unexpectedly humble measurement: the ratio of serum creatinine to body weight.

The study, led by Jiang Mei and colleagues at Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, drew on a longitudinal health examination cohort in China, following 15,442 adults who entered the study with impaired fasting glucose. Over approximately three years of follow-up, 7,230 participants, or 46.8 percent, reverted to normoglycemia. That strikingly high reversion rate alone is worth pausing on, because it underscores how dynamic early dysglycemia really is. The researchers then asked a deceptively simple question: did the creatinine-to-body weight ratio, abbreviated Cre/BW, predict who would cross back over the line?

Creatinine is a waste product generated by muscle metabolism, and because it is cleared by the kidneys at a fairly steady rate, it has long served as a window into both kidney function and, indirectly, muscle mass. Dividing serum creatinine by body weight produces a crude but intriguing index: a person with substantial muscle relative to their body size will tend to have a higher ratio than someone carrying more fat mass for the same weight. In an era when sarcopenic obesity, the combination of reduced muscle and excess fat, is increasingly recognized as a metabolic hazard, such a ratio captures something that body mass index alone cannot.

The statistical machinery behind the study was correspondingly careful. The researchers used Cox proportional hazards models, the standard tool for analyzing time-to-event data, to estimate how the rate of reversion changed with each unit increase in the Cre/BW ratio, multiplied by 100 for numerical convenience. Missing covariate data were handled with multiple imputation across 50 imputed datasets, a robust approach that preserves statistical power while honestly accounting for uncertainty introduced by incomplete records. The fully adjusted model controlled for a battery of potential confounders, meaning the association survived even after accounting for factors that might otherwise explain it away.

The headline result was unambiguous. Each one-unit increase in the Cre/BW ratio was associated with a 34 percent higher rate of reversion to normoglycemia, with a hazard ratio of 1.34 and a 95 percent confidence interval of 1.23 to 1.47. When participants were sorted into quartiles of the ratio, the association rose in a graded fashion across the groups, with a P value for trend below 0.001. In plain terms, the more muscle mass a person appeared to carry relative to their body weight, the more likely their fasting glucose was to return to the normal range within the follow-up window.

But the relationship was not a straight line. Using restricted cubic splines, a flexible modeling technique that allows the shape of an association to bend rather than forcing it into a linear straitjacket, the researchers found statistically significant nonlinearity, with a P value of 0.043. The data revealed an inflection point at a Cre/BW ratio of 1.481, meaning the strength of the association changed character around that threshold. This kind of nonlinear structure matters clinically. If the benefit of a higher ratio plateaus or accelerates at particular values, then a single average effect estimate can mislead, and risk stratification tools built on linear assumptions may misclassify patients near the turning point.

Perhaps the most conceptually interesting part of the study is what happened when the researchers probed why the association exists. They turned to mediation analysis, an exploratory statistical framework that asks whether a third variable lies on the causal pathway between an exposure and an outcome. The mediators they chose were three lipid-related metabolic indices that have become staples of cardiometabolic research: the triglyceride-to-high-density lipoprotein cholesterol ratio, the atherogenic index of plasma, and the triglyceride-glucose index, known as TyG. Each of these captures a different facet of the dyslipidemia and insulin resistance that accompany prediabetes.

The mediation estimates were substantial. The TG/HDL-C ratio statistically accounted for an estimated 28.5 percent of the association between Cre/BW and reversion, while the atherogenic index of plasma mediated an estimated 49.2 percent and the TyG index 49.9 percent. In other words, roughly half of the observed link between the muscle-related ratio and the return of normal blood sugar could be explained statistically by improvements in these lipid-glucose indices. The authors are appropriately cautious here, noting that the mediation findings should be considered exploratory. Mediation analysis in observational data can suggest plausible mechanisms, but it cannot prove causation, and the indices themselves are mathematical composites that may overlap with the outcome measure in complicated ways.

Even with those caveats, the biological story hangs together coherently. Skeletal muscle is the body’s dominant site of glucose disposal, soaking up the majority of circulating glucose after a meal and during fasting through insulin-dependent and insulin-independent pathways. Greater muscle mass relative to body weight implies a larger metabolic sink for glucose and typically better insulin sensitivity. Fat mass, by contrast, particularly visceral fat, promotes insulin resistance and drives the elevated triglycerides and depressed HDL cholesterol that the TG/HDL-C ratio and the atherogenic index of plasma capture. A higher Cre/BW ratio may therefore flag a body composition that favors glucose clearance, and the lipid indices may be the intermediate signature of that favorable physiology.

The findings were consistent across sensitivity analyses, which strengthens confidence that the results are not an artifact of a particular modeling choice. The study is a secondary analysis of anonymized data obtained from the Dryad Digital Repository, so it inherits the limitations of its source cohort, and observational associations of this kind cannot establish that raising one’s creatinine-to-body weight ratio would itself cause reversion to normoglycemia. Still, the work adds to a growing body of evidence that body composition, not just body size, shapes the trajectory of early dysglycemia. For clinicians, the message is that a routine blood test already on nearly every metabolic panel, read alongside body weight, may carry prognostic information about which patients with impaired fasting glucose are positioned to recover. For patients, it reinforces the familiar but newly quantified advice that preserving and building muscle, alongside managing blood lipids, may be among the most powerful levers for pulling blood sugar back from the brink.

Subject of Research: Association of the creatinine-to-body weight ratio with reversion from impaired fasting glucose to normoglycemia and mediation by lipid metabolic indices

Article Title: Creatinine-to-body weight ratio and reversion from impaired fasting glucose to normoglycemia: nonlinear associations and mediation by lipid indices (TyG, TG/HDL-C, AIP)

Article References: Mei, J., Xiao, X., Li, G., Liang, X., Lai, K., Zou, Z., Zhou, Y., Li, Y., & Gui, S. (2026). Creatinine-to-body weight ratio and reversion from impaired fasting glucose to normoglycemia: nonlinear associations and mediation by lipid indices (TyG, TG/HDL-C, AIP). BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02544-z

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02544-z

Keywords: impaired fasting glucose, normoglycemia, creatinine-to-body weight ratio, prediabetes, type 2 diabetes, triglyceride-glucose index, TG/HDL-C ratio, atherogenic index of plasma, insulin resistance, muscle mass, mediation analysis, cohort study