Cadmium, active smoking and renal function deterioration in patients with type 2 diabetes.

BACKGROUND: Cadmium is an established nephrotoxin, present in cigarette smoke. We investigated the hazards of cadmium concentration and smoking status on renal function deterioration. We furthermore discerned whether the association of cadmium concentration with renal function deterioration is attributable to smoking status. METHODS: Prospective analyses were performed in data of 226 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT). Cadmium concentrations were determined from EDTA whole-blood. Smoking status was determined via a self-administered questionnaire. Renal function deterioration was defined as need for renal replacement therapy or a persistent decline of ≥30% in estimated glomerular filtration rate from baseline for at least 3 months. Multivariable Cox regression models were performed to calculate hazard ratios (HRs) for the association between smoking status, cadmium concentration and renal function deterioration. RESULTS: Median (interquartile range) whole-blood cadmium was 2.9 (1.9-5.1) nmol/L. Active smokers had significantly higher cadmium [7.4 (3.3-11.7) nmol/L] compared with never smokers [2.6 (1.6-4.2) nmol/L] and former smokers [2.8 (1.8-4.8) nmol/L]. During median follow-up for 6 (4-8) years, renal function deterioration occurred in 60 persons (27%). Both cadmium and active smoking were associated with an increased hazard for renal function deterioration [HR 1.37, 95% confidence interval (95% CI) 1.06-1.78 and 3.77, 95% CI 1.72-8.29, respectively]. In a multivariable model with both smoking status and cadmium concentration included, active smokers have an increased risk for renal function deterioration (HR 3.00, 95% CI 1.22-7.40), while the association between cadmium and renal function deterioration lost statistical significance (HR 1.16, 95% CI 0.87-1.54). CONCLUSIONS: Active smoking is associated with progressive kidney disease in type 2 diabetes. The association between cadmium concentration and renal function deterioration in large part determined by smoking status. Extensive assessment of smoking status may be useful in patients with type 2 diabetesat high risk of kidney damage.

Clinical and Dietary Determinants of Muscle Mass in Patients with Type 2 Diabetes: Data from the Diabetes and Lifestyle Cohort Twente.

Low muscle mass in patients with type 2 diabetes is associated with a progressively higher risk of morbidity and mortality. The aim of this study was to identify modifiable targets for intervention of muscle mass in type 2 diabetes. Cross-sectional analyses were performed in 375 patients of the Diabetes and Lifestyle Cohort Twente-1 study. Muscle mass was estimated by 24 h urinary creatinine excretion rate (CER, mmol/24 h). Patients were divided in sex-stratified tertiles of CER. To study determinants of CER, multivariable linear regression analyses were performed. Protein intake was determined by Maroni formula and by a semi-quantitative Food Frequency Questionnaire. The mean CER was 16.1 ± 4.8 mmol/24 h and 10.9 ± 2.9 mmol/24 h in men and women, respectively. Lower CER was significantly associated with older age (p < 0.001) as a non-modifiable risk factor, whereas higher BMI (p = 0.015) and lower dietary protein intake (both methods p < 0.001) were identified as modifiable risk factors for lower CER. Overall body mass index (BMI) was high, even in the lowest CER tertile the mean BMI was 30.9 kg/m2, mainly driven by someone's body weight (p = 0.004) instead of someone's height (p = 0.58). In the total population, 28% did not achieve adequate protein intake of >0.8 g/kg/day, with the highest percentage in the lowest CER tertile (52%, p < 0.001). Among patients with type 2 diabetes treated in secondary care, higher BMI and low dietary protein intake are modifiable risk factors for lower muscle mass. Considering the risk associated with low muscle mass, intervention may be useful. To that purpose, dietary protein intake and BMI are potential targets for intervention.

Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake.

OBJECTIVE: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods: We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018. Patients were divided into four groups: <5000, 5000-6999, 7000-9999, ≥ 10,000 steps/day. We studied the association between muscle mass (24 h urinary creatinine excretion rate, CER) and protein intake (by Maroni formula), and the main outcome variable PA (steps/day, Fitbit Flex device) using multivariate linear regression analyses. RESULTS: In the 217 included patients, the median steps/day were 6118 (4115-8638). Of these patients, 48 patients (22%) took 7000-9999 steps/day, 37 patients (17%) took ≥ 10,000 steps/day, and 78 patients (36%) took <5000 steps/day. Patients with <5000 steps/day had, in comparison to patients who took ≥10,000 steps/day, a higher body mass index (BMI) (33 ± 6 vs. 30 ± 5 kg/m2, p = 0.009), lower CER (11.7 ± 4.8 vs. 14.8 ± 3.8 mmol/24 h, p = 0.001), and lower protein intake (0.84 ± 0.29 vs. 1.08 ± 0.22 g/kg/day, p < 0.001). Both creatinine excretion (ß = 0.26, p < 0.001) and dietary protein intake (ß = 0.31, p < 0.001) were strongly associated with PA, which remained unchanged after adjustment for potential confounders. CONCLUSIONS: Prevalent insufficient protein intake and low muscle mass co-exist in obese patients with low physical activity. Dedicated intervention studies are needed to study the role of sufficient protein intake and physical activity in increasing or maintaining muscle mass in patients with type 2 diabetes.

Lifestyle-Related Exposure to Cadmium and Lead is Associated with Diabetic Kidney Disease.

BACKGROUND: Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. MATERIAL AND METHODS: In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. RESULTS: Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78-4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04-0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11-2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02-2.21) and lead (OR 1.83 95% CI: 1.07-3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. CONCLUSIONS: The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.

Requirements of an Application to Monitor Diet, Physical Activity and Glucose Values in Patients with Type 2 Diabetes: The Diameter.

Adherence to a healthy diet and regular physical activity are two important factors in sufficient type 2 diabetes mellitus management. It is recognized that the traditional treatment of outpatients does not meet the requirements for sufficient lifestyle management. It is hypothesised that a personalized diabetes management mHealth application can help. Such an application ideally measures food intake, physical activity, glucose values, and medication use, and then integrates this to provide patients and healthcare professionals insight in these factors, as well as the effect of lifestyle on glucose values in daily life. The lifestyle data can be used to give tailored coaching to improve adherence to lifestyle recommendations and medication use. This study describes the requirements for such an application: the Diameter. An iterative mixed method design approach is used that consists of a cohort study, pilot studies, literature search, and expert meetings. The requirements are defined according to the Function and events, Interactions and usability, Content and structure and Style and aesthetics (FICS) framework. This resulted in 81 requirements for the dietary (n = 37), activity and sedentary (n = 15), glycaemic (n = 12), and general (n = 17) parts. Although many applications are currently available, many of these requirements are not implemented. This stresses the need for the Diameter as a new personalized diabetes application.