Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

Q: What are the key findings of this study?

Young males with hypopituitarism exhibited significantly elevated levels of most amino acids, including glutamate and branched-chain amino acids, which were independently associated with insulin resistance and the presence of NAFLD.

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Hypopituitarism (n=223). Intervention: Hypopituitarism vs. Healthy controls. Primary outcome: Circulating glutamate levels (relative peak area) (p=<0.0001).

Q: What does this research mean for the field?

Young males with hypopituitarism exhibit elevated levels of most amino acids compared to healthy controls, with specific amino acids like glutamate, branched-chain amino acids, and proline being strongly associated with insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To determine whether untreated young males with hypopituitarism show altered amino acid profiles compared to matched controls, and to assess links with insulin resistance, nonalcoholic fatty liver disease, and metabolic syndrome scores.

Yuwen Zhang; Jiting Qiu; Shouyue Sun; Xuqian Fang

doi:10.1007/s00726-024-03429-y

November 23, 2024Amino AcidsOpen Access

Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

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Key result

Hypopituitarism in young males is linked to elevated amino acids associated with insulin resistance and NAFLD.

P<0.0001
n=223

Figures

Why the study?

Changes in amino acid concentrations associated with hypopituitarism remain poorly understood despite the increased risk of NAFLD and insulin resistance in these patients.

Are amino acid profiles altered in young males with hypopituitarism compared to controls, and are they associated with insulin resistance and NAFLD?

Key Points

To determine whether untreated young males with hypopituitarism show altered amino acid profiles compared to matched controls, and to assess links with insulin resistance, nonalcoholic fatty liver disease, and metabolic syndrome scores.
Analyzed amino acid profiles using untargeted metabolomics in 133 young males with hypopituitarism not receiving growth hormone replacement therapy (age 24.5 ± 5.9 years; 57 with NAFLD, 76 without NAFLD).
Compared profiles against 90 age- and BMI-matched healthy controls.
Assessed correlations between amino acid levels and homeostasis model assessment of insulin resistance (HOMA-IR), metabolic syndrome (MetS) scores, and NAFLD presence.
Most amino acids were elevated in subjects with hypopituitarism compared to matched controls.
Glutamate, glutamine, norleucine, and branched-chain amino acids (leucine and valine) correlated with HOMA-IR, with glutamate and norleucine demonstrating independent associations.
Glutamate and proline correlated with MetS scores, whereas alanine and proline linked specifically to the presence of NAFLD.

Study Design

Type

Cross-Sectional (n=223)

Multicenter

No

Structured PICO

Are amino acid profiles altered in young males with hypopituitarism compared to controls, and are they associated with insulin resistance and NAFLD?

P

Population

223 young adult males, including 133 with hypopituitarism off growth hormone replacement and 90 age- and BMI-matched healthy controls, evaluated for amino acid profiles, insulin resistance, and NAFLD.

C

Comparator

90 age and BMI-matched controls

O

Outcome

Amino acid profiles and their association with insulin resistance (HOMA-IR), NAFLD, and Metabolic Syndrome (MetS) scoresurrogate

Main Result

Absolute Event Rate: 6.6% vs 4.1%

p-value: p=<0.0001

Young males with hypopituitarism exhibit elevated amino acid levels, which are associated with insulin resistance and NAFLD.

Limitations

Cross-sectional design limits the ability to establish causal relationships.
Cannot rule out the potential effects of ongoing glucocorticoid, thyroid hormone, and/or sex hormone replacement therapies on amino acid metabolism.
Lack of data on other medications that patients may be taking which could alter amino acid metabolomics.

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Answers are grounded in this paper and cite their sources.

Implication

Does not support routine amino acid assessment in hypopituitarism; leaves open causal links to insulin resistance and NAFLD.

Abstract

Elevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to factors such as visceral obesity, increased insulin resistance (IR), and disturbances in lipid metabolism. However, the changes in AAs concentrations associated with HP remain poorly understood. Therefore, our study aimed to investigate whether individuals with HP, who were not receiving growth hormone replacement therapy (GHRT), exhibited altered AAs compared to controls (CTs), and whether these AAs were associated with IR, the presence of NAFLD, and the Metabolic Syndrome (MetS) score. The AAs profiles of 133 young males with HP (age: 24.5 ± 5.9; 57 with NAFLD and 76 without NAFLD) and 90 age and BMI-matched CTs were analyzed using untargeted metabolomics. The results revealed that most AAs were found to be elevated in subjects with HPs compared to CTs. Glutamate, glutamine, norleucine, and branched-chain amino acids (BCAAs) (leucine and valine) were correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), with glutamate and norleucine showing independent linkage. Glutamate and proline levels were specifically associated with MetS score, while alanine and proline linked to NAFLD. Given that elevated glutamate and BCAAs levels have higher prevalence of NAFLD, we hypothesized that the changes in AAs observed in HPs may be attributed to the impact of NAFLD and IR.

Discussion

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Cite This Study

Zhang et al. (2024) conducted a cross-sectional in Hypopituitarism (n=223). Hypopituitarism vs. Healthy controls was evaluated on Circulating glutamate levels (relative peak area) (p=<0.0001). Young males with hypopituitarism exhibited significantly elevated levels of most amino acids, including glutamate and branched-chain amino acids, which were independently associated with insulin resistance and the presence of NAFLD.

synapsesocial.com/papers/6aaa4ae5504e848891eb8352 https://doi.org/10.1007/s00726-024-03429-y

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Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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