Age-related changes in the diurnal variation of ketogenesis in patients with type 2 diabetes and relevance to hypoglycemic medications

Nakayama, Hitomi; Tokubuchi, Ichiro; Wada, Nobuhiko; Tsuruta, Munehisa; Ohki, Tsuyoshi; Oshige, Tamami; Sasaki, Yuko; Iwata, Shimpei; Kato, Naoka; Ohtsuka, Yoshie; Matsuo, Yuko; Tajiri, Yuji; Yamada, Kentaro

doi:10.1507/endocrj.ej14-0431

Cited by 8 publications

(6 citation statements)

References 35 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we have reported that the plasma levels of 3HB and FFA show marked diurnal fluctuation in patients with type 2 diabetes, with two obvious peaks before breakfast and before dinner. Furthermore, the peak levels were inversely correlated with age 28 . The administration of sulfonylureas or DPP-4 inhibitors was shown to suppress the plasma 3HB levels, likely through their insulinotropic and/or glucagonstatic action.…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

Effects of a sodium glucose co‐transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Yamada

Nakayama

Yoshinobu

et al. 2015

J of Diabetes Invest

Self Cite

View full text Add to dashboard Cite

Aims/IntroductionTo assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.Materials and MethodsWe administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.ResultsContinuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.ConclusionsThe ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.

show abstract

Section: Discussionmentioning

confidence: 93%

“…Furthermore, the peak levels were inversely correlated with age28. The administration of sulfonylureas or DPP-4 inhibitors was shown to suppress the plasma 3HB levels, likely through their insulinotropic and/or glucagonstatic action.…”

Section: Discussionmentioning

confidence: 93%

Effects of a sodium glucose co‐transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Yamada

Nakayama

Yoshinobu

et al. 2015

J of Diabetes Invest

Self Cite

View full text Add to dashboard Cite

show abstract

“…This suggests that 12.1% of those with an EI/BMR <1.35 and ketone body level ≥1.0 mmol/l included underreporters and those who reported extreme energy restriction practices at the time of the dietary survey and blood test. However, because ketone bodies are known to exhibit diurnal variation (24), further investigation is needed to determine the extent to which ketone body values in a single blood sample reflect temporary energy deficits in obese individuals. In recent years, ketone bodies have been measured simply and accurately using small devices (25).…”

Section: Discussionmentioning

confidence: 99%

Relationship between underreporting of energy intake and blood ketone levels in Japanese women with obesity: A retrospective study

et al. 2023

View full text Add to dashboard Cite

Underreporting is a problem in dietary surveys, and data on Japanese individuals with obesity are lacking. In addition, in dietary surveys of individuals with obesity, underreporting and extreme energy restrictive practices for short periods of time have been reported, and blood total ketone levels (ketone bodies) may be able to distinguish between these factors. The present study aimed to examine the relationship between underreporting [energy intake (EI)/basal metabolic rate estimate (BMR)] and ketone bodies in obese Japanese women. The participants included 91 women with obesity aged 47±9 years with a body mass index (BMI) of 29.8±3.9 kg/m² who met the exclusion criteria out of 164 individuals who participated in an institutional cohort study baseline survey between September 2006 and September 2015. The current study defined the relationship between EI/BMR, BMI and the participants' ketone body levels. EI/BMR <1.35 and ketone body level <1.0 mmol/l was defined as underreporters, while EI/BMR <1.35 and ketone body level ≥1.0 mmol/l was defined as energy-restricted reporters based on previous research. The EI/BMR of the participants was 1.44±0.32, and 25.3% had an abnormally high level of ketone bodies. Multiple regression analysis indicated that ketone bodies were explanatory variables for EI/BMR. Analysis using EI/BMR and ketone bodies estimated that 26.4% were underreporters and 12.1% were energy-restricted reporters. There were no significant differences in reported energy intake, carbohydrate intake (g/day), and percentage carbohydrate (%) between the underreporters and energy-restricted reporters. In conclusion, low EI/BMR was associated with high ketone body levels in Japanese women with obesity. The combination of EI/BMR and ketone bodies may distinguish between or screen for underreporters and energy-restricted reporters during a dietary survey.

show abstract

“…The role of metabolites in explaining network differences is more nuanced, and this probably reflects the large biochemical diversity of these molecules [106]. In diseases-specific networks, key differentiating metabolites are ketone bodies, BCAAs, threonine, and tyrosine (in women networks only), and alanine: this can reflect the association with particular diseases, such as type 1 and 2 diabetes mellitus [91,[107][108][109][110], sarcopenia [69,71,72,111] and cognitive impairment [112,113]. Glutamine, glucose, proline, and BCAAs, increasing their metabolic activity, could be biomarkers to predict the emergence of neurodegenerative diseases [114], type 2 diabetes mellitus, and obesity conditions [91,108,109], and sarcopenia [69,71,72].…”

Section: Similarities and Dissimilarities In Different Sex-related Clinical Variables-specific Networkmentioning

confidence: 99%

Lipid and metabolite correlation networks specific to clinical and biochemical covariate show differences associated with sexual dimorphism in a cohort of nonagenarians

et al. 2021

View full text Add to dashboard Cite

This study defines and estimates the metabolite-lipidic component association networks constructed from an array of 20 metabolites and 114 lipids identified and quantified via NMR spectroscopy in the serum of a cohort of 355 Italian nonagenarians and ultra-nonagenarian. Metabolite-lipid association networks were built for men and women and related to an array of 101 clinical and biochemical parameters, including the presence of diseases, bio-humoral parameters, familiarity diseases, drugs treatments, and risk factors. Different connectivity patterns were observed in lipids, branched chains amino acids, alanine, and ketone bodies, suggesting their association with the sex-related and sex-clinical condition-related intrinsic metabolic changes. Furthermore, our results demonstrate, using a holistic system biology approach, that the characterization of metabolic structures and their dynamic inter-connections is a promising tool to shed light on the dimorphic pathophysiological mechanisms of aging at the molecular level.

show abstract

Age-related changes in the diurnal variation of ketogenesis in patients with type 2 diabetes and relevance to hypoglycemic medications

Cited by 8 publications

References 35 publications

Effects of a sodium glucose co‐transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Effects of a sodium glucose co‐transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Relationship between underreporting of energy intake and blood ketone levels in Japanese women with obesity: A retrospective study

Lipid and metabolite correlation networks specific to clinical and biochemical covariate show differences associated with sexual dimorphism in a cohort of nonagenarians

Contact Info

Product

Resources

About