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diabetes mellitus ( dm ) is a chronic progressive disease characterized by hyperglycemia with disturbances of carbohydrate , protein , and lipid metabolism .
dm is the most common endocrine disorder , with an increasing prevalence all over the world . according to data from the u.s .
centers for disease control and prevention , the prevalence of type 1 dm is 0.017% in the united states and about 13 000 americans are diagnosed with type 1 diabetes mellitus every year .
the onset of the disease occurs when the immune system attacks and destroys insulin - producing beta cells found in the pancreas . in this stage , antigen - induced t - lymphocytes and macrophages constantly attack the beta cells [ 36 ] . from the pathological standpoint ,
the basic indicators of insulitis are circulating islet cell antibodies ( ica ) , insulin antibodies ( iaa ) , protein tyrosine phosphatase antibodies ( ia-2 ) , and glutamic acid decarboxylase ( gad ) antibodies .
it is widely accepted that type 1 dm is associated with a genetically determined modification in immunity , which leads to the destruction of pancreatic beta cells .
today , the number of elderly diabetic patients is increasing , mostly because of increased longevity of the diabetic population .
thus , the incidence of microvascular complications ( neuropathy , retinopathy , and nephropathy ) increases with the duration of diabetes , which calls for a solution effective in reducing the incidence of diabetic complications .
the purpose of this study was to determine to what extent the presence of autoimmunity can be used in predicting the development time of microvascular complications .
we included 52 patients with type 1 dm ( based on the american diabetes association s ( ada ) diagnostic and classification criteria   issued in 2007 ) attending the outpatient diabetes clinic of the ministry of health okmeydan training and research hospital between january 2009 and september 2009 .
the subjects had developed microvascular complications ( diabetic retinopathy , diabetic neuropathy , and diabetic nephropathy ) and they had been tested for anti - gad ( glutamic acid decarboxylase ) antibodies and/or islet - cell antibodies ( ica ) .
measurement of anti - glutamic acid decarboxylase antibody ( anti - gad ) in serum was conducted by irma ( immunoradiometric assay ) method and the reference range was accepted as 01 u / ml .
islet cell antibody ( ica ) measurements in serum were done by if ( indirect immunofluorescence ) method with a reference range considered negative .
we recorded patient details such as age , sex , age at disease onset , treatments received for diabetes , as well as other treatments for additional diseases and accompanying diseases ( retinopathy , nephropathy , and neuropathy ) .
development time of microvascular complications was also measured , and patients were compared in terms of autoantibody positivity and development time of microvascular complications .
we measured hemoglobin a1c values by high - performance liquid chromatography ( hplc ) method using a tosoh automated glycohemoglobin analyzer with tosoh hba1c kits and we established the reference range as 4.65.2% . in the evaluation of nephropathy , 24-h urine samples were studied by immunoturbidimetric method using beckman coulter microalbuminuria kits on a beckman coulter syncron lx device .
albumin excretion rates below 30 mg/24-h were considered normoalbuminuria , while levels between 30 and 300 mg/24-h were considered microalbuminuria , and values above 300 mg/24-h were considered macroalbuminuria . the subjects whose test results showed 30 mg/24-h and higher values
at least twice within a 6-month period were defined as microalbuminuric patients . in the evaluation of neuropathy
, we used an electromyography device ( emg )  the nihon kohden - neuropack meb-5504k  and neurologic consultations were obtained .
we used direct fundus examination findings for assessment of diabetic retinopathy following ocular consultations . in the evaluation of retinopathy ,
data was classified as sex , autoantibody existence , microvascular complication development , development time of microvascular complications , and hba1c values .
the data obtained during the study were compared by using student s t - test analysis , because there was no normal distribution .
data was classified as sex , autoantibody existence , microvascular complication development , development time of microvascular complications , and hba1c values .
the data obtained during the study were compared by using student s t - test analysis , because there was no normal distribution .
the study included 52 patients with type 1 dm who developed microvascular complications : 30 females ( 57.7% ) and 22 males ( 42.3% ) .
comparison of mean values within each sex group revealed no statistically significant differences between males and females ( p>0.05 ) .
the mean age of the patients was calculated as 33.948 : 45 . at the diagnosis of diabetes ,
20 patients ( 38.5% of the sample ) tested negative for autoantibodies ( anti - gad and anti - ica ) , while 32 ( 61.5% ) of patients tested positive for anti - gad and/or anti - ica .
thirty - six patients ( 69.2% ) had developed diabetic nephropathy and diabetic retinopathy , 11 patients ( 21.2% ) had diabetic retinopathy , and 5 patients ( 9.6% ) had diabetic neuropathy . in autoantibody - negative patients , the mean hba1c level was 7.7% , while antibody - positive patients had slightly higher hba1c levels ( 7.9% ) , but this difference was not considered statistically significant ( p>0.05 ) .
patients were compared in terms of autoantibody positivity and development time of microvascular complications . the mean time to
onset of diabetes - related microvascular complications in patients with positive autoimmune markers was 11 : 406.46 years .
the mean time to development of microvascular complications in patients with negative autoimmunity was calculated as 10.916.70 years .
when the results of both autoimmunity positive and negative groups were analyzed by student s t - test , no statistically significant difference between the 2 groups was found with respect to the time to development of microvascular complications ( p>0.05 ) ( table 1 ) .
patients with diabetes mellitus may develop chronic hyperglycemia and capillary membrane changes resulting from other metabolic disorders , as well as accelerated atherosclerosis and microvascular and macrovascular complications during the clinical follow - up period [ 814 ] .
today , the longer life expectancy of the diabetic population has significantly increased the incidence and prevalence of diabetes - related chronic complications .
therefore , identifying and addressing the risk factors associated with microvascular complications in type 1 dm and eliminating or reducing the known risks in these patients is crucial .
for this reason , in our study , we focused on the microvascular complications of type 1 dm and examined the role of autoantibodies in patients with type 1 dm on the development time of microvascular complications .
we also aimed to determine whether the presence of autoantibodies is a potentially useful prognostic marker .
there are only a limited number of studies examining the prognostic significance of positivity for autoantibodies [ 1519 ] .
examined the prevalence of gad - ab and icas in 146 insulin - dependent diabetes dm with different disease duration ( 252 years , median 13.2 years ) , and they detected anti - gad positivity as 37% ( 54 of 146 ) and ica positivity as 22% ( 32 of 146 ) , thus concluding that the presence of autoantibodies is not related to the development time of diabetic complications .
zanone et al . reported that autoantibodies to gad were present in 56% of diabetic patients with neuropathy , 57% of long - standing patients without complications , 69% of the short - duration diabetic patients with no complications , 78% of the recently diagnosed diabetic patients , and 13% of the non - diabetic neuropathic patients . in parallel with these results
, they found that there is no correlation between anti - gad antibody positivity and the presence of diabetic neuropathy .
ko et al . examined the relationship between antibodies to gad and diabetic microangiopathic complications in diabetic patients , dividing them into 2 separate groups as anti - gad - positive and anti - gad - negative patients , and they reported that both groups had similar prevalence of microangiopathic complications .
glastras et al . demonstrated that the presence of diabetes - associated autoantibodies did not predict the development of microvascular complications . in our study , we found similar results to those reported in these studies , suggesting that the presence of autoimmunity has no significant effect on the development of microvascular complications in patients with type 1 dm .
szepietowska et al . evaluated the presence of late complications in 41 hospitalized subjects with latent autoimmune diabetes ( lada ) by measuring anti - gad , anti - ica , and anti - ia-2 ( protein tyrosine phosphatase antibodies ) levels , and found a higher incidence of microangiopathy in the autoantibody - positive patients .
their results differ from our findings and from those reported by several of the studies mentioned above .
we did not record and classify the blood pressure , creatinine , antihypertensive therapy , antidiabetic therapy , or body mass index data of the patients .
more accurate results would have been obtained by performing statistical analysis to define more detailed differences between these parameters with positive and negative autoimmunity .
based on our study findings , we can suggest that positivity for autoantibodies associated with type 1 dm plays no significant role in the development time of microvascular complications .
further studies in this field are needed to confirm these findings before a definitive conclusion can be reached .
backgroundtype 1 diabetes mellitus ( dm ) is an autoimmune disease with chronic complications that is becoming more frequent as life expectancy of diabetics has increased owing to improved methods of detection and better management . in this study , we investigated whether the presence of autoimmunity can be used in predicting the development time of microvascular complications.material/methodsour study included 52 patients with type 1 diabetes mellitus ( dm ) . 
 the subjects had developed microvascular complications and they had been tested for anti - gad ( glutamic acid decarboxylase ) antibodies and/or islet - cell antibodies ( ica ) . in the assessment of microvascular complications , we used ocular fundus examination , electromyography ( emg ) , and 24-h urine microalbuminuria tests.resultsof the patients included in the study , 30 were female and 22 were male . 
 of all patients characterized for the existence of diabetic complications , 36 of 52 had both diabetic retinopathy and diabetic nephropathy , 5 patients had diabetic neuropathy , and 11 patients had diabetic retinopathy only . at the diagnosis of diabetes , 20 in 52 patients tested negative for autoantibodies ( anti - gad and anti - ica ) , while 32 of 52 tested positive for anti - gad and/or anti - ica 
 . the mean hba1c level of autoantibody - negative patients was 7.7% , while antibody - positive patients had slightly higher hba1c levels ( 7.9% ) . 
 however , this difference was not statistically significant ( p>0.05 ) . 
 the mean development time of microvascular complications in autoantibody - positive patients was calculated as 11 : 406.46 years , and in patients with negative autoimmunity results it was 10.916.70 years.conclusionsthe presence of diabetes - related autoantibodies ( dras ) in patients with type 1 diabetes mellitus does not have a significant effect on the development time of diabetic microvascular complications .