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Context: Older adults with sarcopenic obesity are at high risk for type 2 diabetes mellitus (T2DM). However, few East Asians have sarcopenic obesity. Since many East Asians have insulin resistance (IR) without obesity, it is possible that older East Asians with sarcopenia and IR might be at high risk for T2DM. However, this relationship has not been studied., Methods: This cross-sectional study included 1629 older adults aged 65 to 84 years registered in the Bunkyo Health Study. All underwent a 75-g oral glucose tolerance test and handgrip strength measurement. Participants were classified into 4 groups by possible sarcopenia (handgrip strength <28 kg in men and <18 kg in women) and IR status (triglyceride glucose [TyG] index ≥8.79 for men and ≥8.62 for women [third quartile]). Modified Poisson regression was used to estimate relative risk (RR) and 95% CIs for T2DM with adjustment for confounding factors., Results: The mean age was 73.1 ± 5.4 years. T2DM was diagnosed in 212 (13.0%) participants. After adjusting for age, sex, body mass index, use of lipid-lowering medications, hypertension, and cardiovascular disease, possible sarcopenia and IR were associated with T2DM, with their coexistence showing a notably stronger association (control: RR, 1.00 [Reference]; possible sarcopenia: RR, 1.55 [95% CI, 1.04-2.30]; IR: RR, 2.69 [95% CI, 1.99-3.65]; and IR possible sarcopenia: RR, 4.76 [95% CI, 3.34-6.79])., Conclusion: Possible sarcopenia based on low handgrip strength and IR based on the TyG index are independently associated with T2DM in older Japanese individuals. Their coexistence shows a particularly strong association with T2DM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65., Objective: To investigate the effects of aging on glucose metabolism after age 65 and to identify its determinants., Methods: This cross-sectional study involved 1438 Japanese older adults without diabetes. All participants underwent a 75-g oral glucose tolerance test (OGTT). Body composition and fat distribution were measured with dual-energy X-ray absorptiometry and magnetic resonance imaging. Participants were divided into 4 groups by age (65-69, 70-74, 75-79, and 80-84 years) to compare differences in metabolic parameters., Results: Mean age and body mass index were 73.0 ± 5.4 years and 22.7 ± 3.0 kg/m 2 . The prevalence of newly diagnosed diabetes increased with age. Fasting glucose, fasting insulin, the area under the curve (AUC)-insulin/AUC-glucose and insulinogenic index were comparable between groups. AUC-glucose and AUC-insulin during OGTT were significantly higher and Matsuda index and disposition index (Matsuda index · AUC-insulin/AUC-glucose) were significantly lower in the age 80-84 group than in the age 65-69 group. Age-related fat accumulation, particularly increased visceral fat area (VFA), and elevated free fatty acid (FFA) levels were observed. Multiple regression revealed strong correlations of both Matsuda index and disposition index with VFA and FFA., Conclusion: Glucose tolerance declined with age in Japanese older adults, possibly due to age-related insulin resistance and β-cell deterioration associated with fat accumulation and elevated FFA levels., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Circulating C-peptide is generally suppressed by exogenous insulin infusion. However, steady-state serum C-peptide (SS SC ) levels during hyperinsulinemic-euglycemic clamp in obese subjects are higher than in healthy subjects, which may contribute to hyperinsulinemia to compensate for insulin resistance. Even in healthy subjects, interindividual variations in SS SC levels are present; however, the characteristics of subjects with high SS SC levels in those populations have not been fully elucidated., Objective: To investigate the clinical parameters associated with interindividual variations in SS SC levels in apparently healthy, nonobese Japanese men., Design and Participants: We studied 49 nonobese (BMI < 25 kg/m 2 ), healthy Japanese men. We evaluated SS SC and insulin sensitivity using hyperinsulinemic-euglycemic clamp with tracer. Intrahepatic lipid (IHL) was measured using proton magnetic resonance spectroscopy., Results: We divided subjects into high and low SS SC groups based on the median SS SC value and compared their clinical parameters. Compared with the low SS SC group, the high SS SC group had IHL accumulation, impaired muscle insulin sensitivity, reduced insulin clearance, and hyperinsulinemia during a 75-g oral glucose tolerance test (OGTT). All of these factors were significantly correlated with SS SC ., Conclusions: In healthy, nonobese men, higher SS SC was associated with impaired muscle insulin sensitivity, IHL accumulation, and hyperinsulinemia during OGTT. These findings suggest that higher endogenous insulin secretion during hyperinsulinemia, along with reduced insulin clearance, may be an early change to maintain metabolic status in the face of moderate muscle insulin resistance, even in healthy, nonobese men.

Context: Asians have a high prevalence of insulin resistance, even in the nonobese state. Whereas both visceral fat accumulation (VFA) and fatty liver (FL) have been shown to be associated with insulin resistance, it is still unclear which is a better marker to predict insulin resistance in nonobese Asians., Objective: The aim of this study was to investigate the relation between VFA or FL and insulin resistance in nondiabetic nonobese Japanese men who do not have diabetes., Design and Participants: We studied 87 nonobese (body mass index <25 kg/m 2 ) Japanese men without diabetes. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity in adipose tissue, muscle, and liver. Intrahepatic lipid and abdominal visceral fat area were measured by 1 H-magnetic resonance spectroscopy and MRI, respectively. Subjects were divided into four groups based on the presence or absence of VFA (visceral fat area ≥100 cm 2 ) and FL (intrahepatic lipid ≥ 5%): control (non-VFA, non-FL; n = 54), VFA only (n = 18), FL only (n = 7), and VFA plus FL (n = 8)., Results: Subjects in the FL only and VFA plus FL groups had insulin resistance in adipose tissue and muscle, as well as relatively lower hepatic insulin sensitivity. The specific insulin sensitivities in these organs were comparable in the VFA only and control groups., Conclusions: In nonobese Japanese men without diabetes, subjects with FL only or VFA plus FL but not VFA only had insulin resistance, suggesting that FL may be a more useful clinical marker than VFA to predict insulin resistance in nonobese Japanese men without diabetes.

Context: Accurate glucagon level measurements are necessary for investigation of mechanisms for postprandial hyperglycemia in type 2 diabetes., Objective: To evaluate the accuracy of postprandial glucagon level measurements using a sandwich ELISA vs a recently established liquid chromatography-high resolution mass spectrometry (LC-HRMS) method in type 2 diabetes mellitus., Design and Participants: Twenty patients with type 2 diabetes treated with insulin underwent a meal test before and after administration of the dipeptidyl peptidase-4 inhibitor anagliptin for 4 weeks. Blood samples were taken serially after the meal, and glucagon levels were measured using both ELISA and LC-HRMS. We compared the change from baseline to 4 weeks ( Δ 0-4W) using the area under the curve for plasma glucagon during the meal test [area under the curve (AUC)0-3h] measured using ELISA and LC-HRMS., Results: ELISA-based glucagon AUC0-3h was higher than LC-HRMS-based AUC0-3h at baseline and 4 weeks. However, differences in Δ 0-4W-AUC0-3h measured using ELISA and LC-HRMS were not statistically significant. Additionally, Δ 0-4W-AUC0-3h measured using ELISA and LC-HRMS were strongly correlated ( r = 0.87, P < 0.001)., Conclusions: Plasma glucagon levels during a meal test in patients with type 2 diabetes measured using ELISA were consistently higher than those measured using LC-HRMS. However, given that the changes in glucagon levels measured using ELISA before and after dipeptidyl peptidase-4 inhibitor therapy were similar to those based on LC-HRMS, this ELISA seems to be useful for evaluating the effect of the drug interventions on postprandial glucagon levels.

Context: Japanese women have substantially lower body mass index (BMI) than women in other developed countries. The BMI of Japanese women has steadily decreased over time. However, glucose metabolism in underweight Japanese women has not been fully characterized., Objective: The aim of this study was to investigate glucose metabolism and the physical characteristics of underweight Japanese women., Design and Participants: We recruited 31 young (20 to 29 years of age) and 30 postmenopausal (50 to 65 years of age) underweight women. We also recruited young normal-weight women (n = 13) and postmenopausal normal-weight women (n = 10) to serve as references. We administered an oral glucose tolerance test (OGTT) and evaluated intramyocellular lipid (IMCL) levels and body composition using 1 H-magnetic resonance spectroscopy and dual-energy X-ray absorptiometry, respectively., Results: Young underweight women had similar glucose tolerance as young normal-weight women. However, postmenopausal underweight women had a higher area under the curve (AUC) for glucose during OGTT than postmenopausal normal-weight women. In postmenopausal underweight women, 2-hour glucose levels during OGTT were negatively correlated with lean body mass ( r = -0.55, P < 0.01) and insulinogenic index ( r = -0.42, P = 0.02) and were positively correlated with IMCL levels ( r = 0.40, P = 0.03). Compared with young underweight women, postmenopausal underweight women had a higher AUC for glucose during OGTT and a lower insulinogenic index and AUC for insulin during OGTT., Conclusions: Postmenopausal underweight women had more impaired glucose tolerance than young underweight women. In postmenopausal underweight women, the degree of glucose tolerance impairment was associated with decreased lean body mass, increased IMCL accumulation, and impaired insulin secretion.