**7. Cytokines**

There is sufficient awareness about diabetes in the community, but not sufficient enough about how pernicious it can be if not controlled. Apprehension of such an ailment should be spread by the health sector as well as the media. Medical camps and general hospitals should ensure the illiterate patients are educated to understand the basic knowledge of health-related issues such as diabetes, and that thorough follow-up with the medication is necessary to sus-

The incidence of infections is increased in patients with diabetes mellitus (DM) [1]. Some of these infections are also more likely to have a complicated course in diabetic than in non-diabetic patients [1]. Diabetic ketoacidosis, for example, is precipitated or complicated by an infection in 75% of the cases. The mortality rate of patients with an infection and ketoacidosis is 43% [1]. In a prospective study of 101,293 adult hospitalised patients, 1640 episodes of bacteraemia were diagnosed. Of 1000 hospitalised patients studied, 2/3 of the bacteraemia were found in patients with DM compared to 1/3 in patients without DM

The immune system can be divided into innate and adaptive-humoral or cellular immune systems. Concerning the humoral adaptive immunity, serum antibody concentrations in patients with DM are normal and they respond to vaccination with pneumococcal vaccine as well as non-diabetic controls [3, 4]. Furthermore, no differences have been shown in the immune response to intramuscular hepatitis B vaccine between children with DM type 1 and controls [5]. Concerning the adaptive cellular immunity, inhibition of the proliferative response to different stimuli has been observed in the lymphocytes of diabetics with poorly controlled disease [6]. An abnormal delayed-type hypersensitivity reaction (cell-mediated immunity)

In a study of 86 DM type 1 patients, 22 (26%) had a serum complement factor 4 concentration (C4) below the normal range [10]. The low C4 values did not appear to be the result of consumption. Since non-diabetic identical twins also had a C4 concentration below normal, and the genes encoding C4 are linked with the antigens DR3 and DR4 (which are expressed in 95% of the Caucasian diabetic patients in contrast to 40% of the general population [6]), the

authors suggest that the reduced C4 level may be an inherited phenomenon [10].

**5. Defects in innate immunity and relation to humoral innate**

has also been described in DM type 1 and type 2 patients [7–9].

tain a healthy lifestyle.

18 Ultimate Guide to Insulin

(*P* < 0.001) [2].

**immunity**

**6. Complement function**

**4. Infection in diabetes**

Studies with whole blood, peripheral blood mononuclear cells (PBMCs), and isolated monocytes of diabetics have to be divided into studies with and without stimulation. Without stimulation, tumour necrosis factor alpha (TNF-α) concentrations in patients with DM type 1 [11], interleukin (IL) 6 concentrations in patients with DM type 2 [12] and IL-8 concentrations in DM type 1 and 2 patients [13] have been studied. Elevated resting values of TNF-α, IL-6 and IL-8 were found in diabetic patients compared to non-diabetic controls.

Studies with PBMCs and isolated monocytes of diabetic patients after stimulation show the following results: in one study [14] the IL-1 secretion of PBMCs in response to lipopolysaccharide (LPS) was reduced in diabetic (type 1 and 2) PBMCs, while the TNF-α response was the same as in the control cells. In another study, monocytes of DM type 1 patients showed a significantly lower production of IL-1 and IL-6, but again no differences in TNF-α concentrations were measured, after stimulation with LPS, compared with monocytes of DM type 2 patients and non-diabetic controls [15]. Possibly most of the TNF-α already disappeared after the incubation period of 24 h [15]. Neither glucose nor insulin showed any effect on the production of IL-1 or IL-6 in isolated monocytes, so the decreased production after stimulation with LPS seemed an intrinsic cellular defect of diabetic cells. It is possible that the elevated resting value of diabetic cells leads to the induction of tolerance to stimulation, which results in lower cytokine secretions after stimulation. This phenomenon has already been described in non-diabetic cells [16].

Studies of cytokine excretion by PBMCs of non-diabetic patients after the addition of different glucose concentrations have shown comparable results as studies with diabetic cells. One study [17] showed that after the addition of different glucose concentrations, unstimulated monocytes of non-diabetics showed an increased TNF-α and IL-6 response. Another study [18] showed that after pokeweed mitogen stimulation, lower IL-2, IL-6 and IL-10 concentrations were found after the addition of glucose (with a dose-response effect). Possibly, the induction of tolerance, described above, can also explain these results. In other words, the presence of glucose leads to a higher resting cytokine production; after stimulation, however, this cytokine production is impaired compared to the situation without glucose. Another substance which may play a role in the increased basal cytokine secretion is the advanced glycation end products (AGEs, which are products of glucose and lysine or arginine residues). An increased formation of AGEs takes place in poorly regulated diabetic patients [19]. Different studies have shown that binding of these AGEs to non-diabetic cells, without stimulation, leads to an increased cytokine production [17, 20, 21]; so, it seemed that the increased formation of these AGEs in diabetics may be responsible for the increased basal cytokine secretion.


**2.2 Dynamic mechanical properties of corroded polymer specimens**

Dynamic mechanical analysis (DMA) was used to investigate the viscoelastic properties of the exposed polymer samples as reported in our previous study [30]. The frequencies under which DMA measurements were made in this study are: 2, 5 and 10 Hz. The loss and storage moduli at low temperatures where polymer molecules are tightly compressed and where the first solid-state transitions occur were analyzed.


*6.1. X-ray Flares*

X-ray flares—flaring and re-brightening behavior in the X-ray emission from GRBs were discovered by the Neil Gehrels *Swift* space observatory [243] and are detected in about a third of *Swift* GRBs [244–249]. They typically display a characteristic shape with a sharp rise in flux followed by a smoother decay, eventually fading back to the pre-flare flux level, and also show a different spectrum (typically harder) compared to the underlying emission. X-ray flares typically occur at times 102 s . *t* . 105 s after the GRB onset. Their temporal and spectral properties appear to be a smooth continuation of the prompt GRB emission spikes [247,248,250]. While during the prompt GRB emission the typical width or spectrum of the different spikes typically does not show a clear systematic evolution, the X-ray flares gradually become wider (with FWHM ∆*t* satisfying ∆*t*/*t* ∼ 0.1 − 0.3), less luminous (h*L*i ∝ *t* −2.7±0.1), and softer with time *t*. Their overall properties strongly suggest that X-ray flares have a common origin with the prompt GRB emission and likely share similar dissipation and/or emission mechanisms.

Therefore, studying the polarization properties of X-ray flares may provide new insights both for their origin, as well as on the emission and/or dissipation mechanisms that are common with the prompt emission. There are some theoretical predictions for their polarization properties e.g., [251,252], but there is still much room for more detailed and realistic predictions that could be tested against future observations. Their observed similarities to prompt GRB pulses suggests that many of the models for prompt GRB polarization may be generalized to apply also for X-ray flares. The fact that X-ray flares last up to hours or sometimes even days after the GRB onset allows pointed observations by sensitive instruments, while their softer spectrum makes them prime targets for future pointed X-ray polarimeters such as eXTP with a polarimetry focusing array at 2–10 keV energies e.g., [198,253].