Decreased serum creatinine to cystatin C ratio is associated with low tongue pressure.

AIM: Tongue strength plays an important role in the process of food intake, and low tongue pressure has been associated with aspiration pneumonia, cognitive decline, and mortality. However, special equipment for tongue pressure measurement is uncommon in general practice. Recently, the serum creatinine-to-cystatin C (Cr/CysC) ratio has been validated as a marker of muscle volume mass. Thus, we aimed to investigate the association of the serum Cr/CysC ratio with tongue pressure in a cross-sectional study. METHODS: This single-center, cross-sectional study enrolled 73 participants (mean age, 71.7 years; men, 49.3%) who regularly attended the hospital for treatment of chronic disease. A tongue pressure of <30 kPa was defined as low tongue pressure. We evaluated the relationships between the serum Cr/CysC ratio and tongue pressure using multiple regression analysis. RESULTS: The serum Cr/CysC ratio was correlated with tongue pressure (R2 = 0.25, P < 0.0001). In multiple regression analyses adjusted for confounders including age, sex, body mass index, and serum albumin, the association remained significant (P = 0.0001). In logistic analyses, the multivariable-adjusted odds ratios of the Cr/CysC ratio for tertiles 1 and 2 compared with tertile 3 for low tongue pressure were 7.81 (95% confidence interval, 1.45-51.73) and 2.71 (95% confidence interval, 0.60-13.19), respectively. CONCLUSIONS: We demonstrated that a decreased serum Cr/CysC ratio was associated with a higher risk of low tongue pressure. Our findings suggest that this simple serum surrogate marker may be a first step toward an intervention for oral function by general practitioners. Geriatr Gerontol Int 2024; 24: 102-108.

Usefulness of urinary tubule injury markers for predicting progression of renal dysfunction in patients with type 2 diabetes and albuminuria: The Fukuoka Diabetes Registry.

AIMS: We prospectively investigated the association of urinary tubule injury markers with estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes. METHODS: Urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty-acid-binding protein (L-FABP), and urinary albumin-to creatinine ratio (UACR) were measured in 2,685 participants with type 2 diabetes. Renal outcomes were ≥ 30% decline in eGFR from the baseline and annual eGFR decline for 5 years. RESULTS: In normoalbuminuric participants, no tubular markers were associated with ≥ 30% decline in eGFR or annual eGFR changes. In those with UACR ≥ 30 mg/gCr, hazard ratios for ≥ 30% eGFR decline were 1.37 (95% confident interval (CI) 1.07-1.75) for urinary KIM-1 (>1.5 µg/gCr), 1.46 (95% CI 1.13-1.66) for urinary NGAL (>16.4 µg/gCr), and 1.26 (95% CI 0.94-1.66) for urinary L-FABP (>12.5 µg/gCr), 2.61 (95% CI 1.64-4.17) for the combination of 3 tubular markers above the cutoff after multivariable adjustments including UACR and eGFR. CONCLUSIONS: The current study demonstrated that urinary tubule injury markers and their combination were significant predictors for the future eGFR decline in those with type 2 diabetes and albuminuria independently of UACR and eGFR. Urinary tubular markers may be useful to identify high-risk patients with albuminuria.

Incidence of end-stage renal disease and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

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 m2, proportion of eGFR < 60 mL/min/1.73 m2 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 m2, 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 m2/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.

Polypharmacy and bone fracture risk in patients with type 2 diabetes: The Fukuoka Diabetes Registry.

AIMS: To prospectively investigate the association between the number of prescribed drugs and the fracture risk in patients with type 2 diabetes. METHODS: Japanese participants with type 2 diabetes (n = 4,706; 2,755 men, 1,951 postmenopausal women; mean age, 66 years) were followed for a median of 5.3 years and grouped on the basis of the number of prescribed drugs at baseline. The main outcomes were fractures at any anatomic site and fragility fractures (fractures at hip and spine sites). RESULTS: During follow-up, any fracture occurred in 662 participants. The overall age- and sex-adjusted fracture incidence rates per 1,000 person-years were 21.2 (0-2 drugs), 28.1 (3-5 drugs), 37.7 (6-8 drugs), and 44.0 (≥9 drugs) (p for trend < 0.001). Compared with 0-2 drugs, the multivariate-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for fractures were 1.34 (1.07-1.68) for 3-5 drugs, 1.76 (1.37-2.26) for 6-8 drugs, and 1.71 (1.27-2.31) in ≥ 9 drugs. The multivariate-adjusted HR (95% CI) per increment in drugs was 1.05 (1.02-1.08) (p < 0.001). Similar tendencies were observed for fragility fractures. CONCLUSIONS: A greater number of prescribed drugs is associated with an increased bone fracture risk in patients with type 2 diabetes.

Constipation and diabetic kidney disease: The Fukuoka Diabetes Registry.

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 m2), 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.

Impact of hip fracture on all-cause mortality in Japanese patients with type 2 diabetes mellitus: The Fukuoka Diabetes Registry.

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.

Prospective study of cancer in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

BACKGROUND: Although the association between type 2 diabetes and cancer has been reported, few epidemiological studies have been conducted in Japanese patients whose leading cause of death is cancer. We prospectively studied the incidence of site-specific cancer, risk factors for developing cancer, cancer death, and survival in Japanese patients with type 2 diabetes. METHODS: We followed 4923 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 99.0%). RESULTS: During the follow-up period, cancer occurred in 450 participants (incidence rate, 22.3/1000 person-years in men and 12.2/1000 person-years in women). In men, prostate cancer was the most common cancer (4.3/1000 person-years), colorectal cancer was the second (3.6/1000 person-years), and gastric cancer was the third (3.3/1000 person-years). In women, colorectal cancer was the most common cancer (2.6/1000 person-years), gastric cancer was the second (2.0/1000 person-years), and breast cancer was the third (1.4/1000 person-years). Smoking, male sex, low-density lipoprotein cholesterol, family history of cancer, and reduced intake of isoflavone daidzein were significant risk factors for developing cancer using multivariable Cox proportional hazards models. The leading cancer death was lung cancer in men and pancreatic cancer in women. The survival was the best for prostate cancer and the worst for pancreatic cancer (2-year cancer-specific survival 95.4%, 30.0%, respectively). CONCLUSIONS: Since the leading cause of death in patients with type 2 diabetes is cancer in Japan, clinicians should be aware of epidemiological data regarding cancer besides diabetic complications.

The serum creatinine to cystatin C ratio predicts bone fracture in patients with type 2 diabetes: The Fukuoka Diabetes Registry.

AIMS: Sarcopenia is involved in the pathogenesis of increased fracture risk associated with diabetes. The serum creatinine to cystatin C (Cr/CysC) ratio has been reported as a surrogate marker for muscle mass. We aimed to prospectively investigate the relationship between the Cr/CysC ratio and fracture risk. METHODS: We followed 1911 postmenopausal women and 2689 men with type 2 diabetes (mean age, 66 years) for a median of 5.3 years, and divided into Cr/CysC ratio quartiles by sex. The primary outcome was fragility fractures and the secondary outcome was any fracture. RESULTS: Fragility fractures occurred in 192 participants, and any fracture occurred in 645 participants. Multivariate-adjusted hazard ratios (95% CI) for fragility fractures were 2.15 (1.19-3.88) (Q1), 1.63 (0.89-2.98) (Q2), 1.34 (0.72-2.51) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 1.75 (0.64-4.50) (Q1), 2.09 (0.83-5.26) (Q2), 1.56 (0.58-4.18) (Q3) and 1.0 (ref.) (Q4) in men. Those for any fracture were 1.46 (1.07-1.98) (Q1), 1.33 (0.98-1.81) (Q2), 1.40 (1.03-1.88) (Q3) and 1.0 (ref.) (Q4) in postmenopausal women, and 2.33 (1.54-3.54) (Q1), 2.02 (1.54-3.04) (Q2), 1.13 (0.71-1.78) (Q3) and 1.0 (ref.) (Q4) in men. CONCLUSIONS: A lower Cr/CysC ratio is a significant risk factor for fractures in patients with type 2 diabetes.

Incidence of diabetic foot ulcer in Japanese patients with type 2 diabetes mellitus: The Fukuoka diabetes registry.

AIMS: Although diabetic foot ulcer (DFU) is a serious diabetic complication, there have been no large-scale epidemiological studies of DFU in Japan. We prospectively investigated the incidences of DFU and limb amputation, the risk for developing DFU, and mortality in Japanese patients with type 2 diabetes. METHODS: We followed 4870 participants (mean age, 65 years) with type 2 diabetes attending an outpatient diabetes clinic for a median of 5.3 years (follow-up rate, 97.7%). The primary outcome was the development of DFU. RESULTS: During the follow-up period, DFU occurred in 74 participants (incidence rate, 2.9/1000 person-years) and limb amputation in 12 (incidence rate, 0.47/1000 person-years). DFU recurrence was observed in 21.4% of participants with history of DFU. History of DFU, chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2), depressive symptoms, and poor glycemic control were significant risk factors for developing DFU. Survival was significantly lower in participants with DFU and/or history of DFU compared with those without (5-year survival rates: with DFU, 87.7%, without DFU, 95.3%; P < .0001). The hazard ratio for death was 1.80 (95% confidence interval, 1.13-2.73, P = .014) in those with DFU and/or history of DFU in a multi-adjusted model. The most common cause of death was cardiovascular disease among participants with DFU, whereas it was malignant neoplasm among those without. CONCLUSIONS: Incidences of DFU and limb amputation were 0.3% and 0.05% per year in this Japanese cohort, respectively. Mortality significantly increased approximately 2-fold in those with DFU and/or history of DFU compared with those without.