• East Asia
• Lifestyle
• large‐scale clinical study

• Humans
• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/epidemiology
• Japan/epidemiology
• Diabetes Complications/epidemiology
• Diabetes Complications/prevention & control
• Life Style
• Asian People
• Risk Factors
• East Asian People

• The Japan Society for the Promotion of Science
• The Ministry of Health, Labour and Welfare, Japan
• The Japan Society for the Promotion of Science
• The Ministry of Health, Labour and Welfare, Japan

• Glucose-lowering drugs
• Systematic review
• Type 2 diabetes

• Humans
• Diabetes Mellitus, Type 2/drug therapy
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use
• Glucagon-Like Peptide-1 Receptor
• Glucose
• Glycated Hemoglobin
• Hypoglycemic Agents/therapeutic use
• Insulin/therapeutic use
• Japan
• Randomized Controlled Trials as Topic
• Sodium
• Non-Randomized Controlled Trials as Topic
• Patient Selection

• Sanofi
• Sanofi

We aimed to explore whether fasting insulin levels correlate with the risk of hypoglycemia in people with Type 2 diabetes (T2D) receiving sulfonylureas (SUs).

Our study included 58 individuals with T2D who had been on treatment with SUs, but not insulin, for more than 2 years. Confirmed hypoglycemic episodes during the past year were self-reported by the patients, and a potential relationship of hypoglycemic event frequency with fasting insulin levels was investigated.

Fasting insulin concentrations were found to have a low positive and statistically significant correlation with the number of cases of mild hypoglycemia per year (ρ = 0.279/P = 0.034) and a moderately positive and statistically significant correlation with the number of severe hypoglycemic events per month (ρ = 0.349/P = 0.007) and per year (ρ = 0.39/P = 0.002).

Our results suggest that fasting insulin levels might be a predictor of the risk of hypoglycemia in people with T2D on treatment with SUs.

• Fasting insulin
• hypoglycemia
• sulfonylureas
• type 2 diabetes

• TNBC (Triple negative breast cancer)
• breast cancer
• insulin
• metabolic health
• metformin

• Body Mass Index
• Breast Neoplasms/etiology
• Breast Neoplasms/metabolism
• Breast Neoplasms/pathology
• Female
• Humans
• Insulin/metabolism
• Obesity/complications
• Oncologists
• Risk Factors

• R01 CA192914 NCI NIH HHS
• R01 CA170851 NCI NIH HHS
• R01 CA158668 NCI NIH HHS
• U01 CA189283 NCI NIH HHS
• P30 CA033572 NCI NIH HHS
• R01 CA155664 NCI NIH HHS
• R01 DK065073 NIDDK NIH HHS

• frailty
• sarcopenia
• sex-related differences
• type 2 diabetes

• Japan Society for the Promotion of Science

• fat oxidation
• glucagon
• ipragliflozin
• sitagliptin
• β-cell function

• Adult
• Aged
• Asian People
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Body Weight/drug effects
• Diabetes Mellitus, Type 2/blood
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Female
• Glucosides/therapeutic use
• Humans
• Japan
• Male
• Middle Aged
• Sitagliptin Phosphate/therapeutic use
• Thiophenes/therapeutic use

• Canagliflozin
• Japanese patients
• macrovascular complications
• major adverse cardiovascular events
• microvascular complications
• sodium-glucose co-transporter 2 inhibitor
• type 2 diabetes mellitus

• Diabetes
• Electronic medical record
• Japan
• Medical informatics
• Registry
• SS-MIX2

• Ministry of Health, Labour and Welfare
• Japan Agency for Medical Research and Development
• The Grant for National Center for Global Health and Medicine
• Japan Science and Technology Agency

[Purpose] This study assessed the effects of type 2 diabetes without diabetic polyneuropathy on muscle strength according to body composition in middle age patients. [Subjects and Methods] This study included 45 non-diabetic individuals (control group) and 50 patients with type 2 diabetes (DM group), 40 to 64 years of age. The body composition was examined, including the leg muscle volume (LMV), which was the sum of the lower-limb muscle mass. The muscle strength was also examined, and the knee extension force (KEF), ankle dorsiflexion force (ADF). The KEF and ADF were normalized to the bodyweight, and the total leg muscle force (TLMF) were calculated by combining the KEF and ADF. The leg muscle quality (LMQ) was calculated as the TLMF normalized with the LMV. [Results] While no significant differences were found in the LMV between groups, the body mass index were higher in the DM group than in the control group. Significant differences were observed in %KEF, %ADF, and the LMQ in the DM group, with 15.8%, 18.7%, and 11.5% lower values than those in the control group, respectively. [Conclusion] The results of this study may demonstrate that muscle weakness occurs before diabetes progresses to a severe condition.

• Diabetes mellitus
• Middle aged
• Muscle weakness

We investigated BMI trajectory patterns before diabetes diagnosis and examined associated changes in visceral adiposity and glucose metabolism. 23,978 non-diabetic Japanese participants (2,789 women) aged 30–64 years were assessed with a mean follow-up of 7.6 years. Diabetes was diagnosed via fasting glucose, HbA_1c, and self-report. Latent-class trajectory analyses were performed to identify BMI trajectories. Longitudinal changes in BMI, visceral adiposity, and glucose metabolism were estimated using mixed models. 1,892 individuals developed diabetes. Three distinct BMI trajectories were identified in adults developing and not developing diabetes, respectively. Among adults developing diabetes, 47.3% were classified as “medium BMI” (n = 895), and had increased mean BMI within the obesity category before diagnosis. The “low BMI” group (38.4%, n = 726) had an initial mean BMI of 21.9 kg/m², and demonstrated small weight gain. The “high BMI” group (n = 271) were severely obese and showed greater increase in BMI until diagnosis. All groups which developed diabetes showed absolute and/or relative increase in visceral fat and impaired β-cell compensation for insulin resistance. All groups not developing diabetes showed measured variables were relatively stable during observation. These data suggest that visceral fat gain may induce β-cell failure in compensation for insulin resistance, resulting in diabetes regardless of obesity level.

• dipeptidyl peptidase-4 inhibitor
• sitagliptin
• obesity

• Aged
• Blood Glucose/drug effects
• Blood Glucose/metabolism
• Body Mass Index
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/epidemiology
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Female
• Glycated Hemoglobin/drug effects
• Glycated Hemoglobin/metabolism
• Humans
• Hypoglycemic Agents/therapeutic use
• Japan
• Male
• Middle Aged
• Obesity/epidemiology
• Prospective Studies
• Sitagliptin Phosphate/therapeutic use

• C-peptide
• postprandial
• type 2 diabetes
• β cell function

Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Although, in contrast to type 1 diabetes, insulin resistance is assumed to be a major pathophysiological feature of T2DM, T2DM never develops unless β-cells fail to compensate insulin resistance. Recent studies have revealed that a deficit of β-cell functional mass is an essential component of the pathophysiology of T2DM, implying that β-cell deficit is a common feature of both type 1 and type 2 diabetes. β-cell dysfunction is present at the diagnosis of T2DM and progressively worsens with disease duration. β-cell dysfunction is associated with worsening of glycemic control and treatment failure; thus, it is important to preserve or recover β-cell functional mass in the management of T2DM. Since β-cell regenerative capacity appears somewhat limited in humans, reducing β-cell workload appears to be the most effective way to preserve β-cell functional mass to date, underpinning the importance of lifestyle modification and weight loss for the treatment and prevention of T2DM. This review summarizes the current knowledge on β-cell functional mass in T2DM and discusses the treatment strategy for T2DM.

• β-cell
• Insulin secretion
• Type 2 diabetes
• Prevention
• Treatment

We aimed to investigate the long-term trajectory of general adiposity assessed by the body mass index (BMI) before the onset of type 2 diabetes in Japanese individuals.

We retrospectively examined data on 1,553 Japanese men without diabetes. Mean BMI and incident cases of diabetes (diabetes indicated by fasting glucose concentrations ≥7.0 mmol/L, a self-reported history of clinician-diagnosed diabetes, or glycated hemoglobin ≥6.5% (≥48 mmol/mol) were assessed on an annual basis over a 10-year period after the baseline examination.

Mean (standard deviation) BMI at the time of diagnosis was 24.4 kg/m² (3.1 kg/m²) among cases of diabetes (n = 191). An increasingly high BMI was associated with the early stage of the disease development, such as an 8- to 10-year prediagnosis period; individuals who developed diabetes experienced a prolonged and stable elevated BMI of ≥24.4 kg/m² over the 8 years before the diagnosis of diabetes. The mean BMI among the non-cases of diabetes did not exceed 23.2 kg/m² throughout the period.

These results suggested that Japanese men who eventually developed diabetes during the 10-year observation period were not characterized as obese, but had stable high-normal BMIs before the onset of diabetes. Previous evidence showed that values for glycemic markers rapidly increased before the development of diabetes; however, the present study showed a slight gain in BMI in the earlier stage of the natural history of diabetes followed by a prolonged period of overweight.

• Body mass index trajectory
• Prediction
• Type 2 diabetes

Since there had been no previous studies of alterations in insulin sensitivity, glucose-stimulated insulin secretion, beta cell function and glucose effectiveness during the development of non-diabetic hyperglycemia in Asian populations, we conducted a longitudinal study of such changes in 244 Japanese adults with normal glucose tolerance (median BMI 23.3 kg/m² and age 51 yrs). The median follow-up period was 3.3 yrs. One hundred and eighty-two subjects maintained normal glucose tolerance (nonprogressors). After excluding the 3 subjects who progressed to diabetes, we analyzed the 59 who developed non-diabetic hyperglycemia (progressors), of which 31 progressed to impaired fasting glucose and 28 to impaired glucose tolerance. Whole body insulin sensitivity was estimated by ISI_Matsuda, glucose-stimulated insulin secretion by [δIRI_0-30/δPG_0-30] and Stumvoll indices, hepatic insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and 1/fasting IRI, beta cell function by oral disposition index (DI_O) ([δIRI_0-30/δPG_0-30]∙[ISI_Matsuda]), and glucose effectiveness by an OGTT-derived index (SgI_O). ISI_Matsuda (p <0.05), [δIRI_0-30/δPG_0-30], DI_O and SgI_O (both p <0.01), but not QUICKI, 1/fasting IRI, or Stumvoll-1st and -2nd phases, were lower in the progressors at baseline. This group was also characterized by the following: 1) ISI_Matsuda, DI_O and SgI_O were reduced by 34%, 32% and 11%, respectively (all p <0.01); 2) QUICKI and 1/fasting IRI diminished by 21% and 5%, respectively (both p <0.01); and 3) no significant changes were found in [δIRI_0-30/δPG_0-30], Stumvoll-1st and -2nd phases or BMI during the follow-up. In the nonprogressors, no indices changed significantly during the follow-up. Our study concluded that during the transition from normal glucose tolerance to non-diabetic hyperglycemia in this non-obese population, whole body insulin sensitivity, hepatic insulin sensitivity, beta cell function, and glucose effectiveness were all attenuated, but no significant changes in glucose-stimulated insulin secretion occurred. Also of note is the fact that the transition took place without any accompanying increase in BMI.

• Beta cell function
• Glucose effectiveness
• Insulin secretion
• Insulin sensitivity
• Non-diabetic hyperglycemia

• Glycemic control
• Insulin
• Sitagliptin
• Type 2 diabetes

• Adult
• Asian People
• Diabetes Mellitus, Type 2/drug therapy
• Drug Therapy, Combination
• Female
• Glycated Hemoglobin/analysis
• Humans
• Hypoglycemic Agents/therapeutic use
• Insulin/therapeutic use
• Male
• Middle Aged
• Prognosis
• Pyrazines/therapeutic use
• Retrospective Studies
• Sitagliptin Phosphate
• Triazoles/therapeutic use