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.

Circulating calprotectin is a potential biomarker for endovascular inflammation in type 2 diabetes mellitus (T2DM). We investigated the determinants of calprotectin and its relationship with the presence of cardiovascular disease (CVD) in 362 T2DM patients included in the Diabetes and Lifestyle Cohort Twente-1 (DIALECT-1) study. Lifestyle exposures, including nutrition, were determined by validated questionnaires. CVD was defined as coronary artery diseases, strokes, and peripheral artery diseases. Median serum calprotectin levels were 1.04 mg/L [IQR: 0.73–1.46 mg/L] and were higher in women (1.11 mg/L) than men (0.96 mg/L, p = 0.007). Current smoking was a major independent determinant of circulating calprotectin, with a 51% higher calprotectin compared to never smoking (p < 0.001). Albuminuria (p = 0.011), former smoking (p = 0.023), and intake of mono- and disaccharides (p = 0.005) also contributed independently to circulating calprotectin. Each incremental increase in calprotectin level was associated with 1.36-times higher odds for CVD (95% CI 1.04–1.77, p = 0.026). In the current study, calprotectin was the only inflammatory parameter significantly associated with CVD. The strong association of circulating calprotectin with smoking, a well-known direct cause of vascular inflammation, and also with CVD, stresses the urge for further research to define its role as a biomarker in T2DM.

OBJECTIVE: To study the prospective association between dietary protein intake and renal function deterioration in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Prospective analyses were performed in data of 382 patients of the Diabetes and Lifestyle Cohort Twente (DIALECT) study. Dietary protein intake was determined by the Maroni equation from 24-h urinary urea excretion. Renal function deterioration was defined as need for renal replacement therapy or a persistent increase of ≥50% in serum creatinine. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the association between dietary protein intake and renal function deterioration. Threshold levels represent the dietary protein intake at which there was a significantly increased and reduced hazard of renal function deterioration. RESULTS: Renal function deterioration occurred in 53 patients (14%), with a median follow-up duration of 6 (interquartile range 5–9) years. Mean dietary protein intake was 91 ± 27 g/day (1.22 ± 0.33 g/kg ideal body weight/day). Dietary protein intake was inversely associated with renal function deterioration (HR 0.62 [95% CI 0.44–0.90]). Patients with an intake 163 g/day had a decreased hazard for renal function deterioration (HR 0.42 [95% CI 0.18–1.00]). Regarding dietary protein intake per kilogram body weight, patients with an intake <1.08 g/kg/day had an increased hazard for renal function deterioration (HR 1.63 [95% CI 1.00–2.65]). CONCLUSIONS: In patients with T2D, unrestricted dietary protein intake was not associated with an increased hazard of renal function deterioration. Therefore, substituting carbohydrates with dietary protein is not contraindicated as a part of T2D management, although it may have a positive effect on body weight while minimizing loss of muscle mass.

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.

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 (β = 0.26, p < 0.001) and dietary protein intake (β = 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.