Tailored therapy in type 2 diabetes:unintended effects of glucose-lowering agents

The clinical treatment landscape of type 2 diabetes has rapidly evolved over the last decades. With the arrival of several new treatment options, the possibility of tailored therapy for patients with type 2 diabetes has become an option. This thesis investigated several advantages and disadvantages of the treatment options. Some of the results contradict with the Dutch treatment guideline, e.g. gliclazide does not seem to better than other sulphonylureas with regard to some important outcomes and there might be role for thiazolidinedionen in the treatment of selected patients. This underlines the importance of tailored therapy. However, this thesis also showed that implementation of tailored therapy is difficult and that there is room for improvement in guidelines and among prescribers

Prediction of impending type 1 diabetes through automated dual-label measurement of proinsulin:C-peptide ratio

Background : The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin: C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release. Methods : Between-day imprecision (n = 20) and split-sample analysis (n = 95) were used to compare TT-TRFIA (Auto Delfia, Perkin-Elmer) with separate methods for proinsulin (in-house TRFIA) and C-peptide (Elecsys, Roche). High-risk multiple autoantibody-positive firstdegree relatives (n = 49; age 5-39) were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range). Results : TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r(2) = 0.96-0.99; P<0.001) with results obtained with separate methods. TT-TRFIA achieved better between-day % CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods). In high-risk relatives fasting PI:C was significantly and inversely correlated ( r(s) = -0.596; P<0.001) with first-phase C-peptide release during clamp ( also with second phase release, only available for age 12-39 years; n = 31), but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release. Conclusions : The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test

The associations of sedentary time and breaks in sedentary time with 24-hour glycaemic control in type 2 diabetes

The aim of this study was to investigate the associations of accelerometer-assessed sedentary time and breaks in sedentary time with 24-h events and duration of hypoglycaemia (7.8 mmol/l) and above target glucose (>9 mmol/l). Thirty-seven participants with type 2 diabetes (age, 62.8 ± 10.5 years; body mass index, 29.6 ± 6.8 kg/m2) in Glasgow, United Kingdom were enrolled between February 2016 and February 2017. Participants wore an activity monitor (activPAL3) recording the time and pattern of sedentary behaviour and a continuous glucose monitoring (CGM, Abbott FreeStyle Libre) for up to 14 days. Linear regression analyses were used to investigate the associations. Participants spent 3.7%, 64.7%, 32.1% and 19.2% of recording h/day in hypoglycaemia, euglycaemia, hyperglycaemia and above target, respectively. There was a negative association between sedentary time and time in euglycaemia (β = -0.44, 95% CI -0.86; -0.03, p = 0.04). There was a trend towards a positive association between sedentary time and time in hyperglycaemia (β = 0.36, 95% CI -0.05; 0.78, p = 0.08). Breaks in sedentary time was associated with higher time in euglycaemia (β = 0.38, 95% CI 0.00; 0.75, p = 0.04). To conclude, in individuals with type 2 diabetes, more time spent in unbroken and continuous sedentary behaviour was associated with poorer glucose control. Conversely, interrupting sedentary time with frequent breaks appears to improve glycaemic control. Therefore, this should be considered as a simple adjunct therapy to improve clinical outcomes in type 2 diabetes

A World history of physical education : cultural, philosophical, comparative

x, 694 p; 23 cm