**15. Disclosure**

some residual insulin secretion, to see whether the treatment could increase C-peptide, but in

Administration of INGAP (islet neogeneis associated protein)in anaimals has caused increased beta cell mass and reversal of hyperglycemia, and hopefully INGAP has regenerating capacity in humans. Daily introductionf of INGAP or placebo has been tried in a double-blind random‐ ized trial in both Type 1 and Type 2 diabetic patients [85], and it showed increased argininstimulated C-peptide during the treatment period, but the effect was very short. Already after 30 days the effect was lost, which does not indicate any influence on beta cell mass as such an

Experimental studies suggest that vitamin D may play a role in the defence against type 1 diabetes as well as type 2 diabetes. Epidemiological data suggest that there is a link between vitamin D deficiency and an increased incidence of Type 1 diabetes. A multinational casecontrol study and a birth cohort follow-up study from Finland [86] have concluded that vita‐ min D3 supplementation at birth protects against type 1 diabetes later in life, and a metaanalysis supports similar conclusions [87]. Low serum levels of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3, calcitriol] has been found in patients with recently diagnosed type 1 diabetes. The protective effects of vitamin D against diabetes are mediated through the regulation of several components such as the immune system and calcium homeostasis. Thus, mechanistic studies show that 1,25(OH)2D3 modulates dendritic cell maturationand facilitates a shift from a Th1 to a Th2 immune response. There is also ncreasingevidence suggesting that vitamin D also affects beta cells directly thereby rendering them more resistant to cellular stress. There are results indicating that Vitamin D may also improve insulin sensitivity, which in turn de‐

Vitamin D has been used in patients with recent onset Type 1 diabetes in an effort to preserve residual insulin secretion. However, so far Vitamin D alone has not been efficacious [88. 89]. It seems resaonable to try Vitamin D, both in higher dose, and in combination with other therapy.

In diabetes, both Type 1 and Type 2, there are signs of inflammation, partly related to gluco‐ tixicity, partly to other traits of the disease. Thus also in Type 1 diabetes there is an inflamma‐ tory componenent in addition to the autoimmune process. IL-1 has been proposed to be of special importance for the destruction of pancreatic beta cells [90], and blocking IL-1 in ex‐ perimental animals has shown important effects on the disease process. Use of IL-1 inhibitor in Type 1 diabetes has shown reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression. These effects suggest that blocking the IL-1beta pathway results in a reduced ability of mononuclear cells

this study the result was negative [84].

504 Type 1 Diabetes

effect should have been much longer

crease beta cell stress.

**13. Anti-inflammatory treatment**

**12. Vitamin D and type 1 diabetes**

Diamyd Medical was sponsor for the Phase II/III GAD-alum trials and has also given financial support for the investigator-initiated mechanistic studies of this type of therapy. Honorarium for lectures has been received from NovoNordisk, Lilly and SanofiAventis. The author is also member of Advisory Board of LifeScan.
