**5. Future studies**

76 Type 1 Diabetes – Complications, Pathogenesis, and Alternative Treatments

14.91%, were recorded. The minimal cluster included 691 AH cases (11.79%), maximal cluster had 570 cases (14.46%), and intermediate cluster included 2898 AH cases (16.02%). The prevalence of AH or proliferative retinopathy (PR) in the maximal or intermediale clusters is greater in relation to the minimal one (Table 7, Fig. 8). Hazard ratios were 1.36 and 1.46 for maximal and intermediale clusters in relation to the minimal cluster, the HR of which was considered as 1. Each year the T1D duration increases the risk of having hypertension. Adjusting according to gender, age and diabetes duration did not significantly change the risk of AH (table 6). Corresponding ORs for AH and PR were 1.36 (95% СІ 1.2-1.54), р<0,001 and 2.04 (95 % СІ 1.72-2.41), р<0.001. It was revealed that T1D prevalence is directly linked to the increase of all-cause and diabetes-related mortality risks,

Hypertension, n

Minimal 5860 691 11.8 11.0-12.6 Intermedial 18095 2898 16.0 15.5-16.6 Maximal 3941 570 14.5 13.4-15.6

Table 7. Prevalence of arterial hypertension in T1D patients in different territorial clusters

Fig. 8. Fraction (%) of patients with proliferative retinopathy (PR) in different clusters of T1D prevalene. The levels of PR prevalence (the dot within the box), its standart errors (the

We have found only one study that compared mortality between populations that differ in prevalence of T1D. This was a joint study of epidemiologists from Finland and Japan (Asao et al., 2003). Previously it was known that the incidence and prevalence of T1D in Finland is several times higher than in Japan, however mortality is higher among Japanese patients. The researchers explain this phenomenon by the fact that Finland was "disturbed" by its world's highest incidence of T1D, and because of that the Finnish health care system has

box height) and 95% CI (lines that emerge) are shown (Khalangot et al., 2009c).

% 95 % СI

as well as to PR and AH prevalence.

(Khalangot et al., 2009c)

T1D prevalence cluster Patients, n Cases of Arterial

Causal link between the territorial distribution of autoimmune T1D in adults and the severity of its course and outcomes remains unknown. The recently discovered antibodies to the type 8 zinc transporter (ZnT8As) have substantially improved the clinical stratification of autoimmune diabetes in adults, demonstrating the link to a more severe insulin deficiency (Lampasone et al., 2010). Swedish researchers point out the possibility of low zinc content in drinking water as a possible T1D risk factor in children (Samuelsson et al., 2010; Haglund et al., 1996). Interestingly, in accordance with our preliminary results (unpublished data), there is no shortage of zinc in blood plasma in adults without diabetes, residing on territories with high prevalence of T1D, and we have even observed an increase of plasma zinc levels among adults with T1D comparing to similar patients from the minimal cluster. Plasma zink levels may be low (T2D) or high (T1D), zink supplementation may improve glycemic control in the two major types of diabetes, however the underlying molecular mechanisms have been elucidated very insignificantly (revieved by Jansen et al. , 2009). It is possible that the study of ZnT8As in

Prevalence of Type 1 Diabetes Correlates with Daily Insulin Dose, Adverse

Vol. 4, p.11.

111, pp. 2927–2934.

51, pp. 3353 – 3361.

72, № 3, pp. 308-314.

539 – 586.

*Diabetes.* Vol. 33, № 3, pp. 271 –276.

*Diabetologia.* Vol. 44, suppl 3, pp. B3-8.

paradox? *Am Coll Cardiol.* Vol. 39, pp. 578-584.

zinc. *Diabetes Care.* Vol. 19, № 8, pp. 873-875.

register. *Diabetes Care.* Vol. 30, № 3, pp. 496-502.

cancer in diabetic patients *BMJ.* Vol. 330, pp. 1304–1305.

sulfonylureas and metformin. *Diabetologia.* Vol. 49, pp. 930–936.

Outcomes and with Autoimmune Process Against Glutamic Acid Decarboxylase in Adults 79

Carstensen B., Kristensen J.K., Ottosen P., Borch-Johnsen K. (2008). On behalf of the steering

group of the National Diabetes Register. The Danish National Diabetes Register: trends in incidence, prevalence and mortality. *Diabetologia.* Vol. 51, pp. 2187-2196. Curtis J.P., Selter J.G., Wang Y., et al. (2005). The obesity paradox: body mass index and outcomes in patients with heart failure. *Arch Intern Med.* Vol. 165, pp. 55-61. Dib SA, Gomes MB. (2009). Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual beta cell function. *Diabetol Metab Syndr.* Vol. 4, № 1, 25 p. Doney A.S., Fischer B., Cecil J.E., Cohen P.T., Boyle D.I., Leese G., Morris A.D., Palmer C.N.

(2003). Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the PPP1R3A locus. *BMC Genet*.

cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: A Go-DARTS Study *Circulation.* Vol.

Becker D.J., Cavender D.E., Drash A.L. (1984). The Pittsburgh insulin-dependent diabetes mellitus (IDDM) morbidity and mortality study. Mortality results.

Committee of the Swedish National Diabetes Register. Glycemic and risk factor control in type 1 diabetes: results from 13,612 patients in a national diabetes

cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with

and treatment of type1 diabetes mellitus. *Verh K Acad Geneeskd Belg*. V. 58, pp.

Diabetes.Trends in the incidence of childhood-onset diabetes in Europe 1989-1998.

term and long-term outcomes after percutaneous coronary intervention: the obesity

between childhood-onset type I diabetes and lowgroundwater concentration of

(2006). Higher prevalence of autoantibodies to insulin and GAD65 in Swedish compared to Lithuanian children with type 1 diabetes. *Diabetes Res Clin Pract*. Vol.

Doney A.S.F., Lee S., Leese G.P., Morris A.D., Palmer C.N.A. (2005). Increased

Dorman J.S., Laporte R.E., Kuller L.H., Cruickshanks K.J., Orchard T.J., Wagener D.K.,

Eeg-Olofsson K., Cederholm J., Nilsson P.M., Gudbjörnsdóttir S., Eliasson B. (2007). Steering

Evans J.M., Donnelly L.A., Emslie-Smith A.M. et al. (2005). Metformin and reduced risk of

Evans J.M., Ogston S.A., Emslie-Smith A., Morris A.D. (2006). Risk of mortality and adverse

Gale E.A.M. (2002) The rise of childhood type 1 diabetes in the 20th Century. *Diabetes.* Vol.

Gorus FK. (1996). The importance of diabetes registries and clinical biology for the study

Green A., Patterson C.C. (2001). EURODIAB TIGER Study Group. Europe and

Gruberg L., Weissman N.J., Waksman R., et al. (2002). The impact of obesity on the short-

Haglund B., Ryckenberg K., Selinus O., Dahlquist G. (1996). Evidence of a relationship

Holmberg H., Vaarala O., Sadauskaite-Kuehne V., Ilonen J., Padaiga Z., Ludvigsson J.

comparison to the levels of zinc in the environment and human body will provide new information about the cause of territorial heterogeneity of T1D.
