The effect of a lifestyle intervention on type 2 diabetes pathophysiology and remission: the Stevenshof pilot study

Although lifestyle interventions can lead to diabetes remission, it is unclear to what extent type 2 diabetes (T2D) remission alters or improves the underlying pathophysiology of the disease. Here, we assess the effects of a lifestyle intervention on T2D reversal or remission and the effects on the underlying pathology. In a Dutch primary care setting, 15 adults with an average T2D duration of 13.4 years who were (pharmacologically) treated for T2D received a diabetes subtyping ("diabetyping") lifestyle intervention (DLI) for six months, aiming for T2D remission. T2D subtype was determined based on an OGTT. Insulin and sulphonylurea (SU) derivative treatment could be terminated for all participants. Body weight, waist/hip ratio, triglyceride levels, HbA1c, fasting, and 2h glucose were significantly improved after three and six months of intervention. Remission and reversal were achieved in two and three participants, respectively. Indices of insulin resistance and beta cell capacity improved, but never reached healthy values, resulting in unchanged T2D subtypes. Our study implies that achieving diabetes remission in individuals with a longer T2D duration is possible, but underlying pathology is only minimally affected, possibly due to an impaired beta cell function. Thus, even when T2D remission is achieved, patients need to continue adhering to lifestyle therapy.Diabetes mellitus: pathophysiological changes and therap

The rhythm of feeding: Effect of nutrients on metabolism and the molecular clock

This thesis describes studies we performed to assess the relationship between nutrients and the circadian clock. We assessed the effects of sugar and fatty acids on the daily rhythmicity of hepatic clock genes and whole-body metabolism in vivo, and on circadian rhythmicity of clock genes in vitro. First, we show in rats that light-phase sugar intake increases food efficiency and body weight compared to light-phase fat intake. Thus, timing of specific macronutrients can affect food efficiency, most likely due to a shifted oxidation pattern. Second, we show an interaction effect of diet timing and composition on hepatic steatosis: consuming a high fat, high sugar diet during the rat’s inactive period resulted in more hepatic fat than consuming the same diet during the dark (active) period. Possibly because the HFHS-light fed animals did not shift their energy expenditure pattern with the shifted time of food intake, resulting in an imbalance between energy intake and expenditure. Next, we investigated in hypothalamic neuronal cells the direct effects of sugar and fat (palmitate) on clock gene rhythms. Palmitate altered the expression profile of the clock gene Bmal1, and sugar altered the expression profile of the clock gene Per2. Taken together, this thesis shows that both fat and sugar affect the hypothalamic clock in a direct manner, independent of caloric content. Furthermore, there is a complementary effect of diet timing and composition on whole-body metabolism and peripheral clock gene expression. These results are important for increasing our understanding of the unhealthy effects of shift work

Assessment of confabulation in patients with alcohol-related cognitive disorders: The Nijmegen-Venray Confabulation List (NVCL-20)

OBJECTIVE: Even though the first awareness of confabulations is often based on observations, only questionnaires and structured interviews quantifying provoked confabulations are available. So far, no tools have been developed to measure spontaneous confabulation. This study describes and validates an observation scale for quantifying confabulation behavior, including spontaneous confabulations, in clinical practice. METHOD: An observation scale consisting of 20 items was developed, the Nijmegen-Venray Confabulation List-20 (NVCL-20). This scale covers spontaneous confabulation, provoked confabulation, and memory and orientation. Professional caregivers completed the NVCL-20 for 28 Korsakoff (KS) patients and 24 cognitively impaired chronic alcoholics (ALC). Their ratings were related to the Dalla Barba Confabulation Battery (DBCB), Provoked Confabulation Test (PCT), and standard neuropsychological tests. RESULTS: The categories of the NVCL-20 have "good" to "excellent" internal consistency and inter-rater agreement. The KS patients confabulated more (both spontaneously and provoked), and more memory and orientation problems were observed. Correlations with neuropsychological test scores showed that confabulations were associated with memory deficits, but not with intrusions or tests of executive dysfunction. CONCLUSIONS: The NVCL-20 is the first instrument that includes items addressing spontaneous confabulation. Administration is reliable, valid and feasible in clinical practice, making it a useful addition to existing confabulating measures