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Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39-81 yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP) and apnea hypopnea index (AHI) were evaluated before and after SGLT2i administration. The relationships between the reduction in AHI and the other variables were examined using Pearson correlation analysis. We have got result that SGLT2i reduced AHI from 31.9 ± 18.0 to 18.8 ± 11.5 events per hr (p = 0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The Pearson correlation analysis showed a significant relationship between the reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.

Osteoporosis not only increases bone fracture risk but also affects survival in postmenopausal women. Although osteoporosis is diagnosed based on low bone mineral density (BMD) determined by dual energy X-ray absorptiometry (DXA), BMD measurement is sometimes difficult because DXA is not widely available in the community. The Fracture Risk Assessment tool (FRAX) can predict 10-year major osteoporotic fracture risk and hip fracture risk with or without femoral neck BMD. The FRAX has not been investigated adequately in community-dwelling Japanese women. We administered the FRAX tool in 13,421 Japanese women who underwent DXA-based forearm BMD measurement in Chiba Bone Survey, a population-based, multicenter, cross-sectional study of postmenopausal osteoporosis conducted in Chiba, Japan. Mean age was 57.77 ± 9.24 years. Mean forearm BMD was 87.94 ± 17.00% of young adult mean (YAM). Mean FRAX major osteoporotic fracture risk without femoral neck BMD was 7.06 ± 5.22%. BMD decreased and percentage of osteoporosis increased from age 55 onward. Age distribution of percentage of subjects with FRAX major osteoporotic fracture risk >15% was similar to that of percentage of osteoporosis subjects. We identified the cutoff value of FRAX major osteoporotic fracture risk for diagnosis of osteoporosis as 7.2%. With this cutoff, the positive likelihood ratio was over 1.0 at age 55 and above but accuracy was low. In conclusion, FRAX without femoral neck BMD reflects bone status, and may be useful to diagnose osteoporosis in Japanese women aged 55 and above, although the sensitivity was low for osteoporosis screening, especially in middle-aged women.

To develop diabetes risk score (RS) based on the current definition of diabetes, we retrospectively analyzed consecutive 4,159 health examinees who were non-diabetic at baseline. Diabetes, diagnosed by fasting plasma glucose (FPG) ≥7.0 mmol/L, 2hPG ≥11.1 mmol/L and/or HbA1c ≥6.5% (48 mmol/mol), developed in 279 of them during the mean period of 4.9 years. A full RS (RS Full ), a RS without 2hPG (RS -2hPG ) and a non-invasive RS (RS NI ) were created on the basis of multivariate Cox proportional model by weighted grading based on hazard ratio in half the persons assigned. The RSs were verified in the remaining half of the participants. Positive family history (FH), male sex, smoking and higher age, systolic blood pressure (SBP), FPG, 2hPG and HbA1c were independent predictors for RS Full . For RS -2hPG , 7 independent predictors, exclusive of 2hPG and smoking but inclusive of elevated triglycerides (TG) comparing to RS Full , were selected. FH, male sex, and higher age, SBP and HbA1c were independent predictors in RS NI . In the validation cohort, C-statistic (95%CI) of RS Full , RS -2hPG and RS NI were 0.80 (0.76-0.84), 0.75 (0.70-0.78) and 0.68 (0.63-0.72), respectively, which were significantly different from each other (P <0.01). Absolute percentage difference between predicted probability and observed diabetes were 1.9%, 0.7% and 0.9%, by the three scores, respectively, and not significantly different from each other. In conclusion, diabetes defined by the current criteria was predicted by the new diabetes risk scores with reasonable accuracy. Nonetheless, RS Full with a postchallenge glucose value performed superior to RS -2hPG and RS NI .

The impact of postchallenge glucose on the relationship between insulin sensitivity (SI) and secretion (β) is unknown. We analyzed data from 2,264 health examinees (male/female 1,524/740, median age 54 yrs) with normal glucose tolerance (NGT, n = 1,623), non-diabetic hyperglycemia (NDH, n = 555), or diabetes (DM, n = 86) using OGTT-derived indices of SI (insulin sensitivity index [ISI]-Matsuda, 1/HOMA-IR, and 1/fasting IRI) and β (δIRI0-30/δPG0-30, and Stumvoll 1st [Stumvoll-1] and 2nd [Stumvoll-2] phases). The combination of 1/HOMA-IR and Stumvoll-1 recapitulated the hyperbolic SI-β relationship with the slope of the fitted line -1.000 in NGT subjects, and therefore it was utilized in the following analysis of the SI-β correlation. In multiple regression analysis of the relationship between SI and β, an independent correlation was found for 1 h-plasma glucose (PG; PG60) but not for 2 h-PG. When the NGT subjects were grouped by PG60 quartile (Q), the fitted line was flat in Q1 but progressively steeper from Q2 to Q4, with a slope (95%CI) of -0.663 (-0.726~-0.605), -0.680 (-0.745~-0.622), -0.847 (-0.922~-0.779), and -1.259 (-1.370~-1.158) (P for trend < 0.05). The fitted line steepened further in the NDH and DM groups, with a slope of -1.545 and -1.915, respectively (P < 0.01 for the difference). The intercept of the fitted line for SI-β correlation was also progressively lower across the PG60 Q for NGT, NDH, and DM. In conclusion, using the 1/HOMA-IR-Stumvoll-1 pair for an analysis of the SI-β relationship, elevated PG60 was associated with steepening and downward shifting of the fitted line for the SI-β correlation. The finding suggests impaired beta cell function.

The risk factors for impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have yet to be established. Our aim was to elucidate the predisposing factors for IFG and IGT in Japanese subjects with normal glucose tolerance (NGT). Using a 75 g oral glucose tolerance test (OGTT), we analyzed 604 adults with the ADA-defined NGT. Follow-up glucose tolerance status was determined by 75 g OGTT performed 3.7 yrs later. Glucose-stimulated insulin secretion (GSIS), whole body insulin sensitivity (SI) and beta cell function (BCF) were estimated by Stumvoll indices, ISI(Matsuda), and a product of Stumvoll 1(st) and ISI(Matsuda), respectively, and hepatic SI by quantitative insulin sensitivity check index. Logistic regression analysis revealed that attenuated BCF due to low GSIS was an independent risk factor for IFG. Low whole body SI was an additional risk for IGT. Male gender and high BMI were independently related to the progression to both IFG and IGT, whereas a positive diabetes family history was independently related to IGT. The worsening of glucose tolerance at large was predicted with 66% sensitivity by risk engine with GSIS, whole body SI, gender, BMI and glucose. This finding may help when implementing early intervention strategies for diabetes.

The aim of this study was to assess the changes in insulin secretion and insulin sensitivity in relation to fasting and 2-hour plasma glucose (PG) levels and to assess the independent contributions of their impairments to non-diabetic hyperglycemia. A total of 2157 Japanese workers (mean age 52.6±7.3 years and mean BMI 23.9±3.2 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Of these subjects, 1125 had normal glucose tolerance (NGT), 525 subjects had isolated impaired fasting glucose (IFG), 159 subjects had isolated impaired glucose tolerance (IGT), 263 subjects had combined IFG and IGT, and 85 subjects had newly diagnosed type 2 diabetes. Insulinogenic index and Matsuda insulin sensitivity index (ISI) were significantly attenuated in subjects with normal but slightly elevated fasting PG, or in subjects with normal but slightly elevated 2-hour PG. Whereas, InsAUC(120)/GluAUC(120) was not significantly decreased in those subjects, and significant decrease of it was observed exclusively in subjects with abnormal fasting PG (≥ 106 mg/dL) or abnormal 2-hour PG (≥ 221 mg/dL). Using multiple regression analyses, both Matsuda ISI and insulinogenic index were independently correlated with PG concentrations in subjects with IFG and/or IGT, while Matsuda ISI alone was independently correlated with fasting PG concentrations in normoglycemic subjects. In conclusion, both insulinogenic index and Matsuda ISI were significantly attenuated in subjects with normal but slightly elevated PG. Lowering of Matsuda ISI was likely to be a strong contributor to 'elevation of fasting PG within the normal range' in this population.