Increased cancer mortality among Japanese individuals with hyperinsulinemia.

AIMS: To evaluate the effect of hyperinsulinemia on cancer death, we clarified the association between hyperinsulinemia and cancer mortality among Japanese individuals. METHODS: All the participants (5586 men and 6652 women) lived in Hiroshima City, underwent a 75 g oral glucose tolerance test between 1994 and 2012, and were followed for mortality until August 2013. A systematic review of death certificates was used to confirm the cause of death. RESULTS: During the follow-up period (median, 10.0 years), 587 participants died of cancer. Lung cancer was the most common cause of organ-specific death. We divided the participants into 3 groups according to the tertiles of fasting immunoreactive insulin (FIRI) levels (low, middle, and high groups). The high group had the highest mortality rate (5.5 per 1000 person-years). The hazard ratio (HR) for cancer mortality of the high group after adjustment for possible confounders, such as age, sex, body mass index, smoking status, alcohol intake, and radiation effects (model 1), was significantly higher than that of the low group (HR, 1.55; 95% confidence interval (CI), 1.23-1.95). In model 2 (model 1 plus fasting plasma glucose) and model 3 (model 1 plus HbA1c), the multivariate HRs for cancer mortality were 1.46 (95% CI, 1.15-1.85) and 1.48 (95% CI, 1.17-1.87), respectively.The HR for cancer death at high FIRI levels (per 1 µU/mL) was 1.04 (95% CI, 1.02-1.05) in all participants after adjusting for fasting plasma glucose level and other confounders. In the subgroup analysis, the HRs were 1.03 (95% CI, 0.98-1.09), 1.05 (95% CI, 1.02-1.08), and 1.04 (95% CI, 1.02-1.06) in the normal, prediabetes, and diabetes group, respectively. CONCLUSIONS: Hyperinsulinemia was associated with a high risk of cancer mortality and may be an important link between cancer mortality and diabetes or prediabetes.

Association between a biomarker of glucose spikes, 1,5-anhydroglucitol, and cancer mortality.

INTRODUCTION: 1,5-Anhydroglucitol (1,5-AG) is a biomarker of glucose spikes. To evaluate the effect of acute glucose excursions on cancer death, we clarified the association between 1,5-AG and cancer mortality among Japanese individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: We measured 1,5-AG in 6783 (2842 men, 3941 women) individuals with normal fasting and 2-hour plasma glucose who received a 75 g oral glucose tolerance test between 1994 and 2012. They were followed for mortality until August 2013. A systematic review of death certificates was used to confirm the cause of death. We divided the participants into four groups according to the quartile of 1,5-AG level at registration. We used Cox regression to clarify the association between 1,5-AG levels and cancer mortality with multivariate adjustment for possible confounders. RESULTS: During the follow-up period (median, 10.0 years), 140 men and 109 women died of cancer. The HR for cancer mortality of the lowest quartile group was higher than that of the highest quartile group in men (HR, 2.62; 95% CI, 1.60 to 4.41) and in women (HR, 1.47; 95% CI, 0.88 to 2.47). These associations were not attenuated with further adjustment for HbA1c. CONCLUSIONS: 1,5-AG was associated with high risk of cancer mortality in Japanese men after adjustment for HbA1c.

Longitudinal examination of pancreatic ß-cell function in Japanese individuals.

AIMS/INTRODUCTION: We carried out a retrospective, longitudinal analysis of ß-cell function between a diabetes mellitus group, including those that progressed to diabetes mellitus during the follow-up period, and a diabetic type with glycated hemoglobin (HbA1c) <6.5 group, including those that progressed to a diabetic type during the follow-up period. ß-Cell function was assessed using homeostasis model of assessment of ß-cell function. MATERIALS AND METHODS: The relationship between the duration of diabetes mellitus or the diabetic type and pancreatic ß-cell function was compared between the diabetes mellitus group (1,817) and diabetic type with HbA1c <6.5 group (1,843) using results from an oral glucose tolerance test. Linear mixed effects models were used to analyze repeated measurements of oral glucose tolerance tests. RESULTS: The slope of the regression line of ß-cell function for the duration of the diabetes mellitus group was -2.2%/year before the diagnosis. The slope differed after the diagnosis, and the difference was 1.3. The slope of the diabetic type group was -1.2%/year, and no significant difference was observed in the slope before and after the diagnosis. ß-Cell function at the onset was 54.3% in the diabetic type group and 40.6% in the diabetes mellitus group, and the slope of the regression line was significantly higher in the diabetes mellitus group. We divided the diabetes mellitus and diabetic type with HbA1c <6.5 groups into obese and non-obese participants. ß-Cell function declined more with obesity. CONCLUSIONS: Subsequent declines in ß-cell function were faster in the diabetes mellitus group than that in the diabetic type with HbA1c <6.5 group, and increased with obesity.

Association of type 2 diabetes and an inflammatory marker with incident bone fracture among a Japanese cohort.

AIMS/INTRODUCTION: There are various causes of incident bone fracture. Not only aging, low bone mineral density and history of previous fracture, but also diabetes mellitus and inflammation are regarded as risk factors for fracture. The purpose of the present study was to verify the association of glycemic control or one inflammatory marker with incident fracture in a large-scale Japanese cohort. MATERIALS AND METHODS: The present study was carried out at the Hiroshima Atomic Bomb Casualty Council and included 6,556 participants (2,785 men and 3,771 women, aged 55-87 years) who underwent annual health examinations and were followed for 7.4 years. Information about incident fractures was collected at interviews. Participants were classified into three groups: normal, borderline and diabetes mellitus according to glycohemoglobin levels (treated diabetes patients were included in the diabetes mellitus group). Furthermore, participants were classified into four additional groups by glycemic control (diabetes mellitus or non-diabetes mellitus) and C-reactive protein (CRP) levels (low or high). Hazard ratios (HRs) of diabetes mellitus, CRP and their combined risk of incident fracture were evaluated. RESULTS: After adjusting for age, bone mineral density and previous fracture, CRP was associated with increased fracture risk (in men HR 1.04, 95% confidence interval [CI]: 1.003-1.06; in women HR 1.07, 95% CI: 1.03-1.13), and diabetes mellitus predicted fracture risk in men (HR 1.31, 95% CI: 1.02-1.51). Fracture risk was significantly higher among the diabetes mellitus with high CRP group compared with the non-diabetes mellitus with low CRP group (in men HR 1.47, 95% CI: 1.02-1.98; in women HR 1.41, 95% CI: 1.04-1.92). CONCLUSIONS: Among a Japanese cohort, CRP measurements were helpful to detect high fracture risk in patients with type 2 diabetes mellitus.

Evaluation of the new criteria of 2010 for diabetes mellitus: Japan Diabetes Society.

We investigated the characteristics of the new criteria for diabetes mellitus (DM) issued by the Japan Diabetes Society in 2010, which include HbA1C measurement, and differences between 1999 criteria, in order to indicate clinical caution points. If a person with fasting plasma glucose (FPG) ≥126 mg/dl or an oral glucose tolerance test (OGTT) 2-h value ≥200 and HbA1C ≥6.5 % is determined as having DM, the disease can be detected at a rate of ≥70 % in persons <60 years and at no more than 40-50 % in elderly persons. In longitudinal examination, we observed that individuals with DM with FPG ≥126 mg/dl and HbA1C ≥6.5 % obtained the same determination over time at a rate of nearly 90 %. The percentage of persons whose result shifted from normal type to DM was 3- to 4-fold lower than that of persons whose result shifted from normal type to diabetic type. Based on these results, measurement of FPG and HbA1C at the same time may be extremely effective in identifying DM, although we should pay attention to a higher likelihood that mild glucose metabolism disorders will be overlooked.

Low high-density lipoprotein cholesterol level is a significant risk factor for development of type 2 diabetes: Data from the Hawaii-Los Angeles-Hiroshima study.

AIMS/INTRODUCTION: A low level of high-density lipoprotein cholesterol (HDLC) is a common feature of metabolic syndrome. We have reported that Japanese-Americans who share a virtually identical genetic makeup with native Japanese, but who have lived Westernized lifestyles for decades, have lower HDLC levels and a high prevalence of type 2 diabetes compared with native Japanese. However, the impact of low HDLC level on type 2 diabetes is unclear. The aims of the present study were to evaluate whether serum HDLC level was associated with development of type 2 diabetes and if the effect might be modified by lifestyle. MATERIALS AND METHODS: We examined 1,133 non-diabetic Japanese-Americans and 1,072 non-diabetic Japanese, who underwent the 75-g oral glucose tolerance test (OGTT) and were followed for an average of 8.8 and 7.0 years, respectively. We analyzed whether serum HDLC level is a risk factor for development of type 2 diabetes based on the Cox proportional hazards model. RESULTS: After adjustment for age and sex, hazard ratios for development of type 2 diabetes per unit of serum HDLC level (mmol/L) were 0.292 (95% confidence interval [CI] 0.186-0.458, P < 0.0001) among Japanese-Americans and 0.551 (95% CI 0.375-0.88, P = 0.0023) among native Japanese. Comparable hazard ratios after further adjustment for category of OGTT and body mass index were 0.981 (95% CI 0.970-0.993, P = 0.0018) and 0.991 (95% CI 0.980-1.002, P = 0.112), respectively. CONCLUSIONS: HDLC level was associated with development of type 2 diabetes in both Japanese-Americans and native Japanese. However, these results suggest that the impact of high-density lipoprotein on glucose metabolism might be affected by lifestyle.