MTNR1B genotype and effects of carbohydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial

Heianza, Yoriko; Zhou, Tao; Wang, Xuan; Furtado, Jeremy D.; Appel, Lawrence J.; Sacks, Frank M.; Qi, Lu

doi:10.1007/s00125-023-06056-6

Cited by 3 publications

(5 citation statements)

References 44 publications

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“…Fasting and 120-minute glucose concentrations did not differ from those observed in people without diabetes-associated variation in rs10830963. A lack of effect on 120-minute glucose is congruent with reports from several other similarly powered cohorts [ 8 , 19 ].…”

Section: Discussionsupporting

confidence: 89%

“…Twenty subjects had the GG genotype, and the remaining 126 had the CG genotype. The latter 2 genotypes were combined into 1 group as has been done before [ 19 ]. Age, weight, body composition, and fasting glucose did not differ between genotype groups.…”

Section: Resultsmentioning

confidence: 99%

“…The recent report by Heianza et al examining the effect of diabetes-associated genetic variation on glucose tolerance in the MTNR1B locus did not show an effect on β-cell function. This raised the possibility that effects of this variant on fasting and postprandial glucose concentrations are mediated through effects on α-cell function [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, there were no observable effects on insulin secretion as measured by the insulinogenic index. In addition, overall β-cell function quantified by a disposition index (DI) (insulinogenic index * Matsuda index) was not associated with the SNP [ 19 ].…”

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confidence: 99%

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Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function

Vella,

Mohan,

Christie

et al. 2024

Journal of the Endocrine Society

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Context Multiple common genetic variants have been associated with type 2 diabetes but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes. Objective To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes. Design The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose and Disposition Indices were measured using the oral minimal model. Setting The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN. Participants Two cohorts were utilized for this analysis: one cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank. Intervention Two-hour, 7-sample OGTT Main Outcome Measures Fasting, nadir and integrated glucagon concentrations. Results One or 2 copies of the G-allele at rs10830963were associated with increased post-challenge glucose and glucagon concentrations compared to subjects with the CC genotype. Conclusions The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function

Vella,

Mohan,

Christie

et al. 2024

Journal of the Endocrine Society

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“…Acting as an important modulator of glucose production and insulin sensitivity [ 42 ], the relationship of MLT with T2DM has been investigated. It has been reported that the polymorphisms of MLT receptor are associated with different glycaemic responses after consuming a diet with high carbohydrates and high glycaemic index levels [ 43 ] and might be a genetic candidate for the development of T2DM [ 44 ]. Moreover, higher levels of MLT have been demonstrated to be significantly associated with a lower risk of T2DMs [ 45 ], and a lower abundance of MLT has been reported in T2DM patients, without or with complications [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

He,

Yu,

Chen

et al. 2024

Journal of Diabetes Research

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Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients.Methods: One hundred twenty‐six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C‐reactive protein (CRP), Interleukin 6 (IL‐6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function‐Adult Version (BRIEF‐A) and the Epidemiological Research Center Depression Scale (CES‐D), respectively.Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF‐A and CES‐D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF‐A and CES‐D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients.Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM‐associated executive impairment and depression status.

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MTNR1B-Genotyp beeinflusst glykämische Reaktion auf Kohlenhydrate

2024

Diabetologie und Stoffwechsel

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Die Variante rs10830963 des Gens für den Melatoninrezeptor MTNR1B gilt als Risikofaktor für die Entstehung eines Typ-2-Diabetes und spielt zudem für die zirkadiane Rhythmik eine wesentliche Rolle. Heianza et al. wollten prüfen, inwieweit die Aufnahme von Kohlenhydraten und der glykämische Index (GI) in Interaktion mit dem o.g. Genotyp die glykämische Reaktion beim Glukosebelastungstest beeinflussen, und haben eine randomisierte Studie initiiert.

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MTNR1B genotype and effects of carbohydrate quantity and dietary glycaemic index on glycaemic response to an oral glucose load: the OmniCarb trial

Cited by 3 publications

References 44 publications

Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function

Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

MTNR1B-Genotyp beeinflusst glykämische Reaktion auf Kohlenhydrate

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