Aims/hypothesis
Our aim was to compare the contributions of impaired beta cell function (IBF) and insulin resistance with the development of type 2 diabetes in a Japanese community.
Methods
A total ...of 2094 residents aged 40–79 years without diabetes underwent a health examination including a 75 g OGTT in 2007. Participants were divided into four groups according to the presence or absence of IBF (insulinogenic index/HOMA-IR ≤28.5) and insulin resistance (HOMA-IR ≥1.61) and were followed up for 7 years (2007–2014). Cox’s proportional hazards model was used to estimate HRs and 95% CIs for type 2 diabetes. The population attributable fractions (PAFs) due to IBF, insulin resistance, and their combination were calculated.
Results
At baseline, the prevalence of isolated IBF, isolated insulin resistance, and both IBF and insulin resistance were 5.4%, 24.1% and 9.5%, respectively. During the follow-up period, 272 participants developed type 2 diabetes. The multivariable-adjusted HRs (95% CI) and PAFs (95% CI) for type 2 diabetes were 6.3 (4.3, 9.2) and 13.3% (8.7, 17.7) in the participants with isolated IBF, 1.9 (1.3, 2.7) and 10.5% (4.0, 16.6) in those with isolated insulin resistance, and 8.0 (5.7, 11.4) and 29.3% (23.0, 35.1) in those with both IBF and insulin resistance, respectively, compared with the participants without either.
Conclusions/interpretation
The present study suggests that the combination of IBF and insulin resistance makes the main contribution to the development of type 2 diabetes in Japanese communities.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Constipation was shown to be associated with higher risk of end-stage kidney disease or incident chronic kidney disease, although evidence in diabetic patients is lacking. The objective of ...the present study was to examine the association between constipation and diabetic kidney disease (DKD).
Methods
In total, 4826 Japanese outpatients with type 2 diabetes were classified according to presence or absence of constipation (defecation frequency < 3 times/week and/or taking laxative medication). DKD was defined as presence of decreased estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m
2
), and/or albuminuria (urinary albumin-to-creatinine ratio ≥ 30 mg/g). Odds ratios for the presence of DKD were computed by a logistic regression model.
Results
Compared with participants without constipation, the age- and sex-adjusted odds ratio for presence of DKD was 1.58 (95% confidence interval 1.38–1.82) for those with constipation. This association persisted following adjustment for potential confounding factors. Decreased defecation frequency and laxative use were also significantly associated with higher prevalence of DKD. Overall, these findings were identical even when decreased eGFR and albuminuria were separately analyzed.
Conclusions
Constipation was associated with higher likelihood of DKD in patients with diabetes, suggesting the importance of clinical assessment of constipation to identify patients at high risk of progression of kidney disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Epidemiological data regarding diabetic kidney disease are accumulated insufficiently in Japan. We prospectively investigated the incidence of end-stage renal disease (ESRD) and risk ...factors for progression of renal dysfunction in Japanese patients with type 2 diabetes.
Methods
4904 participants with type 2 diabetes (mean age 65 years, mean estimated glomerular filtration rate (eGFR) 75 mL/min/1.73 m
2
, proportion of eGFR < 60 mL/min/1.73 m
2
21%) were investigated for the progression to ESRD requiring dialysis in multicenter outpatients registry for 5 years. Risk factors for progression of renal dysfunction (≥ 30% decline in eGFR from the baseline and annual eGFR decline rates) were evaluated.
Results
The incidence rates of ESRD and all-cause mortality were 4.1/1000 person-years and 12.3/1000 person-years, respectively, and increased according to stages of chronic kidney disease (eGFR < 30 mL/min/1.73 m
2
, incidence of ESRD 176.6/1000 person-years, all-cause mortality 57.4/1000 person-years). Incidence of ≥ 30% decline in eGFR from the baseline was 16.4% at 5 years, and the mean annual decline rate was −1.84 mL/min/1.73 m
2
/year. The progression of renal dysfunction was significantly associated with older age, poor glycemic control, blood pressure, albuminuria, eGFR, previous cardiovascular disease, lifestyle factors (body mass index, reduced intake of dietary fiber, increased intake of sodium, no regular exercise), and depressive symptoms.
Conclusions
This prospective study has emphasized the importance of multifactorial interventions on risk factors to suppress the high incidence of ESRD in Japanese patients with type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Context
Although recent genetic studies have identified many susceptibility loci associated with type 2 diabetes (T2D), the usefulness of such loci for precision medicine remains uncertain.
...Objective
This study investigated the impact of genetic risk score (GRS) on the development of T2D in a general Japanese population.
Participants
The current study consists of 1465 subjects aged 40 to 79 years without diabetes who underwent a health examination in 2002.
Design
The GRS was generated using the literature-based effect size for T2D of 84 susceptibility loci for the Japanese population, and the risk estimates of GRS on the incidence of T2D were computed by using a Cox proportional hazard model in a 10-year follow-up study. The influence of GRS on the predictive ability was estimated with Harrell C statistics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI).
Results
During the 10-year follow-up, 199 subjects experienced T2D. The risk of developing T2D increased significantly with elevating quintiles of GRS (multivariable-adjusted hazard ratio for the fifth vs first quintile, 2.85; 95% CI, 1.83 to 4.44). When incorporating GRS into the multivariable model comprising environmental risk factors, the Harrell C statistics (95% CI) increased from 0.681 (0.645 to 0.717) to 0.707 (0.672 to 0.742) and the predictive ability of T2D was significantly improved (IDI, 0.0376; 95% CI, 0.0284 to 0.0494; cNRI, 0.3565; 95% CI, 0.1278 to 0.5829). GRS was also associated with the risk of T2D independently of environmental risk factors.
Conclusions
These findings suggest the usefulness of GRS for identifying a high-risk population together with environmental risk factors in the Japanese population.
The genetic risk score generated for type 2 diabetes improved the predictive ability of incident type 2 diabetes from a model with environmental risk factors in a general Japanese population.
Aims/Introduction
The evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with ...diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.
Materials and Methods
A total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m2 were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m2 during the follow‐up period.
Results
During follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m2. Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m2 with no coffee consumption, −1.89 mL/min/1.73 m2 with less than one cup per day, −1.80 mL/min/1.73 m2 with one cup per day and −1.78 mL/min/1.73 m2 with two or more cups per day (P for trend 0.03).
Conclusions
Coffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.
Higher coffee consumption was significantly associated with reduced risk of chronic kidney disease development in patients with type 2 diabetes. The protective effect of coffee consumption on chronic kidney disease was stronger in subgroups of patients with poor glycemic control and longer diabetes duration.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community.
A total of 2,253 ...community-dwelling Japanese individuals aged 40-79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87-2.10, 2.11-5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed after ingestion of l-theanine-rich green tea products containing 8 mg of l-theanine by 12 healthy volunteers.
During follow-up, 282 subjects developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes decreased significantly with elevating levels of serum ethylamine (
for trend = 0.04). This association remained unchanged after adjusting for potential confounding factors. The multivariable-adjusted hazard ratio (HR) for type 2 diabetes was significantly lower in the fourth quartile of serum ethylamine than in the first quartile (HR 0.69, 95% CI 0.49-0.98). This trend of decrease in diabetic risk across serum ethylamine levels was more prominent in middle-aged subjects and in subjects with prediabetes, obesity, or insulin resistance. Kinetic analysis estimated that the minimum concentration at the steady state was >5.90 ng/mL in the case of twice-daily ingestion with an interval of 12 h.
Higher serum ethylamine was significantly associated with lower risk of the development of type 2 diabetes in a general Japanese population. The measurement of serum ethylamine concentration would be a useful biomarker for the objective estimation of l-theanine consumption.
Aims/Introduction
The incidence of severe hypoglycemia and its risk factors including an insulin‐sensitizing adipokine, adiponectin, were prospectively investigated in Japanese patients with type 1 ...or insulin‐treated type 2 diabetes.
Materials and Methods
A total of 207 participants with type 1 diabetes (mean age 55 years) and 1,396 with insulin‐treated type 2 diabetes (mean age 65 years) from the local diabetes registry were followed for 5 years (follow‐up rate 99%). Severe hypoglycemia was defined as events requiring the assistance of others for recovery from hypoglycemia.
Results
The incidence of severe hypoglycemia was 9.2 per 100 person‐years in those with type 1 diabetes, and 2.3 per 100 person‐years in those with insulin‐treated type 2 diabetes, respectively. For type 1 diabetes, the risk was significant in those with a history of severe hypoglycemia within the previous year, slow eating and higher serum adiponectin (the highest vs the lowest in quartile hazard ratio 2.36, 95% confidence interval 1.22–4.69). For insulin‐treated type 2 diabetes, the risk included age ≥65 years, history of severe hypoglycemia within the previous year, alcohol consumption ≥60 g/day, larger insulin dose and higher serum adiponectin (the highest vs the lowest in quartile, hazard ratio 2.95, 95% confidence interval 1.22–4.69). For all participants, the incidence of severe hypoglycemia increased along with serum adiponectin (age‐ and sex‐adjusted hazard ratio 1.65 per 1 standard deviation increase of log serum adiponectin, 95% confidence interval 1.45–1.87).
Conclusions
The incidence of severe hypoglycemia was prospectively determined, and the association between severe hypoglycemia and higher serum adiponectin was observed in Japanese patients with type 1 and insulin‐treated type 2 diabetes.
The incidence of severe hypoglycemia was prospectively determined in Japanese patients with type 1 and insulin‐treated type 2 diabetes. The development of severe hypoglycemia was associated with higher serum adiponectin level.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aims/Introduction
Patients with type 2 diabetes mellitus have an increased hip fracture risk. We investigated the relationship between hip fracture and all‐cause death in patients with type 2 ...diabetes in comparison with cardiovascular disease (CVD) or end‐stage renal disease (ERSD).
Materials and Methods
In total, 4,923 Japanese participants with type 2 diabetes (mean age 65 years, 2,790 men, 2,133 women) were followed for a median of 5.3 years (follow‐up rate 99.5%). We evaluated the associations between the presence of hip fracture (n = 110), upper limb fracture (n = 801), CVD (n = 1,344), ESRD (n = 104) and all‐cause death by logistic regression analysis.
Results
A total of 309 participants died during follow up. Multivariate‐adjusted odds ratios (ORs) for all‐cause mortality were significantly higher in participants with hip fractures than those without hip fractures (OR 2.67, 95% confidence interval CI 1.54–4.41), whereas the ORs for upper limb fracture were not significant. The ORs for all‐cause mortality were significantly higher in participants with CVD than those without CVD (OR 1.78, 95% CI, 1.39–2.70) and ESRD (OR 2.36, 95% CI 1.32–4.05). The ORs for all‐cause mortality of hip fracture were not affected by further adjustment for CVD and ESRD (OR 2.74, 95% CI 1.58–4.54). The cause of death was infection (40.0%), malignant neoplasm (25.0%) and CVD (15.0%) among participants with hip fracture.
Conclusions
Hip fractures were associated with an increased risk of death among Japanese patients with type 2 diabetes, independently of CVD and ESRD.
Hip fracture is associated with increased mortality in the general population, although few studies have investigated the impact of hip fractures on the risk of death in patients with type 2 diabetes who also have a higher prevalence of fatal diseases, such as cardiovascular disease, renal disease or malignant neoplasia. In this study, the presence of hip fracture was associated with an increased risk of death among Japanese patients with type 2 diabetes, independently of cardiovascular disease and end‐stage renal disease. It should be emphasized that hip fracture is a critical event in the aging population of patients with type 2 diabetes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aims/Introduction
A younger age at menarche is associated with obesity and type 2 diabetes in adult life. The impact of early‐onset menarche on obesity and glycemic control in type 2 diabetes has not ...been investigated. The present study examined the relationship between age at menarche and obesity and glycemic control in type 2 diabetes.
Materials and Methods
A total of 2,133 patients with type 2 diabetes aged ≥20 years were divided into groups according to age at menarche (≤11, 12, 13, 14 and ≥15 years). A retrospective cohort study examined the association of menarcheal age with adiposity and hemoglobin A1c.
Results
Age at menarche was inversely associated with body mass index (BMI) and abdominal circumference (P < 0.001). Each 1‐year decrease in age at menarche was associated with a 0.25‐kg/m2 and 0.6‐cm increase in BMI and abdominal circumference, respectively, using a multivariate‐adjusted model. Odds ratios for obesity and abdominal obesity significantly increased in participants with age at menarche ≤11 years after multivariable adjustments when age at menarche of 13 years was used as the reference (odds ratio 1.95, 95% CI 1.33–2.88, odds ratio 1.95, 95% CI 1.32–2.87, respectively). Younger age at menarche was significantly associated with higher hemoglobin A1c (P < 0.001); however, the association was not statistically significant after adjusting for BMI.
Conclusions
Age at menarche of ≤11 years was associated with obesity after adjusting for confounding factors, and poor glycemic control associated with high BMI in type 2 diabetes. Age at menarche should be considered during clinical assessments.
Age at menarche was inversely associated with obesity after adjusting for confounding factors, and poor glycemic control associated with BMI in type 2 diabetes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins' interaction with ...paraoxonase (PON)1 enzyme polymorphism.
Adult Japanese type 2 diabetes patients (n = 3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA
, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups.
Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA
, and with increased serum C peptide and HOMA2-%β (all P < 0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P < 0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations.
Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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