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In the two present prospective cohort studies we conducted on population-based sample from the North-eastern adult Germans, the following main results were obtained. First, CP had a moderate effect on CVD and all-cause mortality [93]. In further analyses, we investigated the association of CP and mortality considering DM as a mediator in the CP-Mortality association. We did not, however, come up with enough evidence supporting this hypothesis. Furthermore, no substantial evidence was found on our hypothesis suggesting a joint effect of CP and DM on mortality [93]. Second, we studied the causal effect of CP on diabetes incidence or long-term change of Hba1c level using 11-years of follow-up data from SHIP. However, our data did not indicate any independent effect of CP on the incidence of diabetes mellitus after comprehensive confounder adjustment using DAGs. Models that consider baseline periodontal status effect on long term change of Hba1c revealed similar non-significant results [94].
Introduction: Patients who are overweight or obese have an increased risk of developing type 2 diabetes mellitus (T2DM). Weight loss can have a positive effect on glycemic control. Objective: We aimed to investigate glycemic control in patients with T2DM and overweight or obesity during a structured weight-loss program. Methods: This was a prospective, interventional study. We recruited 36 patients (14 men and 22 women) with a median age of 58.5 years and median body mass index (BMI) of 34.1, to a 15-week structured weight-loss program with a low-calorie (800 kcal) formula diet for 6 weeks. The primary end point, HbA<sub>1c</sub> level, and secondary end points, anthropometric data, medication, and safety, were assessed weekly. Laboratory values and quality of life were assessed at baseline and after 15 weeks. Results: HbA<sub>1c</sub> decreased from 7.3% at baseline to 6.5% at 15 weeks (p < 0.001), median body weight by 11.9 kg (p < 0.001), median BMI by 4.3 (p < 0.001) and median waist circumference by 11.0 cm (p < 0.001). Two participants discontinued insulin therapy, 4 could reduce their dosage of oral antidiabetic agents, and 6 completely discontinued their antidiabetic medication. Insulin dose decreased from 0.63 (0.38–0.89) to 0.39 (0.15–0.70) units/kg body weight (p < 0.001). No patient experienced hypoglycemic episodes or hospital emergency visits. Triglycerides and total cholesterol decreased as well as surrogate markers of liver function. However, the levels of high-density and low-density lipoprotein cholesterol (HDL-C and LDL-C) as well as uric acid remain unchanged. Regarding quality of life, the median physical health score increased from 44.5 (39.7–51.4) at baseline to 48.0 (43.1–55.3; p = 0.007), and the median mental health score decreased from 42.1 (36.1–46.7) to 37.4 (30.3–43.7; p = 0.004). Conclusions: A structured weight-loss program is effective in the short term in reducing HbA<sub>1c</sub>, weight, and antidiabetic medication in patients with T2DM who are overweight or obese. Levels of HDL-C and LDL-C were not affected by short-term weight loss. The decline in mental health and the long-term effects of improved glycemic control require further trials.
The development of the two main types of diabetes mellitus, type 1 and type 2 (T1D, T2D), is closely associated with the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in insulin-secreting pancreatic β-cells. In T1D, β-cell death
is triggered by proinflammatory cytokines, which mainly lead to the formation of ROS
in mitochondria and RNS in the cytosol. Pancreatic β-cells are extraordinarily sensitive
to oxidative stress due to their low glutathione peroxidase and catalase expression.
Thus, hydrogen peroxide (H2O2) cannot be detoxified, neither sufficiently, nor rapidly.
H2O2 itself is a rather weakly reactive ROS but can react in the Fenton reaction to form
highly reactive hydroxyl radicals (●OH), that can damage cells in a variety of ways and
induce cell death. The cell and its organelles are bounded by biological membranes
that differ in their permeability to H2O2. Aquaporins (AQPs) are water-transporting
transmembrane proteins, and some isoforms have been shown to facilitate a bidirectional transport of H2O2 across cellular membranes in addition to water. The role of
AQP8 was investigated in an insulin-producing cell model by stably overexpressing
AQP8 (AQP8↑) and by a CRISPR/Cas9-mediated AQP8 knockout. However, AQP8
proved to be an essential protein for the viability of the insulin-producing RINm5F cells, and so we established a tet-on-regulated AQP8 knockdown (AQP8 KD). Our results highlight that AQP8 is involved in H2O2 transport across the plasma and mitochondrial membranes, and that AQP8 expression gets upregulated by proinflammatory cytokines (in vitro) and in an acutely diabetic rat model (in vivo). Furthermore, it was shown that the increased proinflammatory cytokine toxicity is due to enhanced mitochondrial oxidative stress, because H2O2 cannot be efficiently transported in AQP8 KD cells and ●OH
are increasingly generated. Caspase activity then raises, and apoptosis is increasingly
induced coupled with a proportion of ferroptosis-mediated cell death because of a concomitant decrease in nitric oxide (NO●) concentration. In conclusion, AQP8 is localized in the plasma and mitochondrial membrane of insulin-producing RINm5F cells, where it is involved in H2O2 transport. In T1D, AQP8 plays an important role in the transport of H2O2 from the mitochondrial matrix to the cytosol so that the concentration is lowered in the mitochondria. This wider distribution of H2O2 may ease the inactivation of H2O2.