Ozone therapy and viscosity of blood and plasma, distance of intermittent claudication and certain biochemical components in patients with diabetes type II and ischemia of the lower extremities]

Blood and plasma viscosity, total blood lipids, triglycerides, total cholesterol, free fatty acids, fibrinogen, hematocrit, and lipidogram were determined in patients with diabetes mellitus type II and coexisting symptoms of the obliterative arteriosclerosis of the lower limbs. Intermittent claudication distance has been measured parallel. The same tests have been carried out after ozone therapy. A significant improvement in the intermittent claudication and reduction in blood and plasma viscosity have been noted. There was statistically significant correlation between intermittent claudication decrease and blood viscosity reduction following ozone therapy.     

Various parameters of lipid metabolism after intra-arterial injections of ozone in patients with ischemia of the lower extremities and diabetes mellitus

In 50 subjects with arteriosclerotic ischaemia of the lower extremities and 41 subjects with diabetes mellitus ozone was applied intra-arterially. Before and after the treatment serum lipids concentration was examined. In the group with arteriosclerotic ischemia significant decrease in cholesterol level and both his fractions was seen. Whereas in the group with diabetes the cholesterol LDL was significantly reduced. In both groups total lipids level serum was decreased. It suggests that ++ozone therapy set back the arteriosclerosis progress, normalized some parameters of lipid metabolism and improved HDL to LDL cholesterol fractions relationship.     

Homocysteine and cystatin C level changes in haemodialysed patients and connection with cerebro- and cardiovascular complications

Plasma homocysteine and Cystatin C levels of 360 chronic haemodialysed patients were measured in fasting (191 men, mean age: 55.5 years; and 169 women, mean: 62.9 years). The patients were divided into subgroups: diabetes mellitus (34 men and 38 women 7 vs 8 IDDM). obliterative arteriosclerosis (68 men and 61 women), cardiovascular complications (75 men and 84 women) and stroke (16 men and 12 women), and after renal transplantation in chronic rejection (15 men and 5 female). Homocysteine was determined by IMx analyser from Abbott by FPIA method. Immunoturbidimetric method was used for quantification of Cystatin C (PETIA). The lowest Cystatin C concentration was found in diabetic patients (4.35 +/- 0.15 mg/l in men and 3.18 +/- 1.77 mg/l in women) and the highest one occurred in anuric and bilateral nephrectomised and transplanted chronic rejected patients (6.075 mg/l in men and 6.35 mg/l in women: p<0.001). The homocysteine levels (24.98 +/- 2.94 micromol/l in men and 23.88 +/- 1.76 micromol/l in women) exceeded the upper limit of reference range (<15.0 micromol/l). There was a significant difference in favour of subgroup of cardiovascular (27.25 micromol/l in men and 26.87 micromol/l in women) and stroke patients (27.16 micromol/l in men and 30.76 micromol/l in women p<0.001). Elevated levels were found in chronic rejected patients with accelerated arteriosclerotic events (25.94 micromol/l in men and 27.43 micromol/l in women). Good positive linear correlation was found between serum homocysteine and Cystatin C levels (r=0.2393 and 0.2252). The authors demonstrated hyperhomocysteinaemia associated with high Cystatin C concentration in four subgroups of haemodialysed patients (obliterative and accelerated arteriosclerosis, cardiovascular disease, and cerebrovascular complications and stroke).     

The effect of pramlintide (amylin analogue) treatment on bone metabolism and bone density in patients with type 1 diabetes mellitus.

Amylin is a 37-amino-acid peptide related to CGRP and calcitonin. It is co-secreted with insulin from pancreatic beta-cells. Amylin is deficient with type 1 diabetes mellitus. To study the in vivo effects of amylin in humans, diabetic patients are an adequate model of chronic amylin deficiency. We investigated the effect of a 12 months pramlintide therapy (amylin analogue) on bone metabolism in patients with type 1 diabetes mellitus. 23 patients with type 1 diabetes mellitus (age 45.2 +/- 10.3 years, duration of diabetes mellitus 20.7 +/- 9.8 years, 13 male, 10 female) injected themselves 0.1 ml pramlintide, a human amylin analogue, four times per day for a period of 12 months. Bone mineral density measurements of the lumbar spine by dual-energy X-ray absorptiometry (DXA), and biochemical markers of bone metabolism (serum-calcium, PTH, osteocalcin, urinary pyridinium cross-links) were obtained before and one year after starting pramlintide therapy. None of the following parameters changed significantly: bone density, serum calcium, PTH, osteocalcin or pyridinium cross-links. Only osteocalcin decreased from 7.205 ng/ml to 5.825 ng/ml, but this change was not statistically significant. We conclude that a one-year pramlintide therapy does not affect bone density or bone metabolism in patients with type 1 diabetes mellitus without osteopenia (based on the markers used).     

Cytochemical indices of leukocytes in patients with diabetes mellitus

Cytochemical indices of leukocytes were determined in 16 patients with diabetes mellitus in the period of unbalancing and balancing. The following tests were made: content of glycogen and lipids, acid phosphatase (AP), alkaline phosphatase (AIP), myeloperoxidase (MPO) and nonspecific alpha-naphtol acetate esterase (NANAE) activity. In unbalanced diabetics an evident decrease in the activity of AP and MPO could be noted as well as a decrease of glycogen content and an increase of lipid content. An insignificant decrease could be observed in the activity of ALP and NANAE in granulocytes. A slight increase in the activity of NANAE in monocytes would be found. Balancing this disease induced the increase of all parameters in granulocytes except MPO activity. It is interesting to note that balancing diabetes mellitus deepened the observed changes in the decrease or increase of tested parameters. The presented findings clearly indicate the role of metabolic disorders in diabetes mellitus on the activity of some neutrophilic enzymes and the glycogen and the content of lipids in neutrophils.     

Hyperuricemia is independently associated with coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus

Aims

To investigate the relationship between hyperuricemia (HUA) and the clinical backgrounds in Japanese patients with type 2 diabetes mellitus.

Methods

After a cross-sectional study evaluating the association of HUA with the clinical characteristics in 1,213 patients with type 2 diabetes mellitus, the estimated glomerular filtration rate (eGFR) and the incidence of diabetic macroangiopathies was investigated in a prospective observational study in 1,073 patients during a 3.5 year period. HUA was defined by serum uric acid levels >327 μmol/L or as patients using allopurinol.

Results

The frequency of HUA was significantly higher in the diabetic patients (32% in men and 15% in women) than in the normal controls (14% in men and 1% in women). In total, HUA was found in 299 (25%) of the patients during the cross-sectional study. Even after adjusting for sex, drinking status, treatment for diabetes mellitus, body mass index, hypertension, use of diuretics, hyperlipidemia, HbA1c and/or the eGFR, the HUA was independently associated with some diabetic complications. The eGFR was significantly reduced in HUA patients compared to those with normouricemia in the 12 months after observation was started. HUA was also an independent risk factor for coronary heart disease even after adjustment in the Cox proportional hazard model.

Conclusions

HUA is a associated with diabetic micro- and macroangiopathies. HUA is a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. However, the influence of HUA is considered to be limited.     

Glucose tolerance disorders in patients with cancer of the colon

Relating to the Williams' report suggesting twofold higher incidence of diabetes mellitus in patients with the cancer of the colon, the study aiming at comparing an incidence of diabetes mellitus in patients with stomach, lung, and colon malignancies were carried out. Coexistence of the above listed neoplasms with diabetes mellitus type II was assessed in patients hospitalized at the Department of Gastroenterology and Metabolic Diseases, Institute of the Internal Diseases, Medical Academy in Warsaw within 1978-1986. Moreover, glycaemia and insulinemia curves were plotted following oral glucose load (75 g) in 16 patients with the cancer of the colon and 15 patients without malignancy. Only patients with body weight not exceeding 10% of the normal body weight, without history of diabetes mellitus and not treated with corticosteroids were classified for the study. Mean glycaemia and insulinemia values did not differ statistically in the investigated groups except statistically significantly higher serum insulin level in patients with cancer of the lung in the thirties minute of the test. Differences statistically significant were also not observed in retrospective analysis. However, an incidence of diabetes mellitus in patients with the cancer of the colon was 10.5% being higher than mean incidence of diabetes mellitus in this age group. Moreover, glucose load test has shown tolerance abnormalities in 4 patients with cancer of the colon, 1 patient with cancer of the lung, and 1 patient without malignancy. The obtained results indicate tendency to higher incidence of carbohydrate metabolism disorders in patients with cancer of the colon.     

Disorders of colonic motility in patients with diabetes mellitus

Motility disturbances of the colon can give significant symptoms in patients with diabetes mellitus. Constipation is a common complaint in these patients. Diarrhea associated with a generalized autonomic neuropathy can be very troublesome. There is a disturbance in the gastrocolonic response to eating in patients with diabetes mellitus who have constipation. These patients have no postprandial increase in colonic motility. However, their colonic smooth muscle contracts normally to the exogenous administration of neostigmine or metoclopramide. Stool softeners used in combination with the smooth muscle stimulants (neostigmine or metoclopramide) are helpful in treating constipation in patients with diabetes mellitus. Diarrhea can be treated with loperamide or diphenoxylate. Biofeedback may be useful in treating incontinence associated with diarrhea in these patients.     

Increased Risk of Acute Pancreatitis in Patients with Type 2 Diabetes: An Observational Study Using a Japanese Hospital Database

Background

Increased risks of acute pancreatitis in patients with type 2 diabetes mellitus have been reported recently in several countries. We aimed to estimate the risks of acute pancreatitis in Japanese patients with diabetes mellitus.

Methods/Findings

We examined a large-scale hospital administrative database consisting of one million patients in 16 secondary medical care hospitals, from 2003 to 2010. The incidence rates of acute pancreatitis were estimated with cohort design; the odds ratios associated with diabetes mellitus and other comorbid risk factors were estimated with separate case-control analyses.In cohort analysis, the incidence of acute pancreatitis was higher in 14,707 diabetic patients than in 186,032 non-diabetic patients (4.75 vs. 1.65 per 1,000 patient-years) and increased in male patients and as age advanced. The adjusted odds ratio of acute pancreatitis in patients with diabetes mellitus was 1.86 (P<0.001) compared with non-diabetic patients in case-control analysis from 1,372 cases and 5,469 matched controls, which is consistent with the ones reported in previous studies. Alcoholism and gallstones were associated with a large increase in the risk of acute pancreatitis (adjusted odds ratio 13.40 and 14.29, respectively, P<0.001), although dyslipidemia was associated with significant risk reduction (adjusted odds ratio 0.62, P<0.001).

Conclusions

This observational study ascertained the elevated incidence rates and risk of acute pancreatitis in Japanese patients with diabetes. The risk estimates in Japanese patients with diabetes were in agreement with the ones reported in previous studies, and the elevated risk of acute pancreatitis in patients with diabetes would be generalized in different locations/populations.     

Diabetes mellitus in patients with aneuploid chromosome aberrations and in their parents

Summary The frequency of chemical diabetes is increased in patients with aneuploid sex chromosome aberrations such as Klinefelter's syndrome and Turner's syndrome, and a high frequency of chemical diabetes has been found in parents of patients with Down's syndrome. Abnormal pattern in plasma insulin and growth hormone during a glucose load has been found in patients with Klinefelter's syndrome and Turner's syndrome.These findings might, if they are confirmed on large and well selected groups of patients with different chromosome abnormalities, shed some new light on the genetic background of diabetes mellitus, i.e. on the role of the sex chromosomes in the aetiology of diabetes mellitus or alternatively on the possibility that the frequency of non-disjunction in increased in patients with diabetes mellitus.     

Polymorphic gene markers of lipid metabolism are associated with diabetic nephropathy in patients with type 1 diabetes mellitus

In groups of type 1 diabetes mellitus patients with and without clinical signs of diabetic nephropathy (n = 62 and n = 68, respectively), a search was made for associations between diabetic nephropathy and the polymorphic marker epsilon2/epsilon3/epsilon4 of apolipoprotein E gene (APOE), I/D marker of apolipoprotein B gene (APOB), and Ser447Ter marker of lipoprotein lipase-encoding gene (LPL). The risk of diabetic nephropathy was higher in the carriers of allele epsilon3 and genotype epsilon3/epsilon3 of the polymorphic marker epsilon2/epsilon3/epsilon4 of APOE gene as well as in the carriers of allele 1 and APOB genotype/gene (OR = 2.08 and 2.16; 1.91 and 2.11, respectively). Conversely, the carriers of allele D showed a reduced risk of this complication (OR = 0.52). No significant differences in distribution of alleles and genotypes of the polymorphic marker Ser447Ter of LPL gene were found between the groups. Our results indicate that the genes encoding two major components of lipid metabolism are involved in the development of diabetic nephropathy in patients with type 1 diabetes mellitus.     

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism

Background

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Little is known about the management and long-term glycaemic control of CHI patients with diabetes after pancreatic surgery. We searched the German/Austrian DPV database and compared the course of 42 CHI patients with diabetes to that of patients with type 1 diabetes mellitus (T1DM). Study groups were compared at diabetes onset and after a follow-up period of 6.1 [3.3–9.7] (median [interquartile range]) years.

Results

The majority of CHI patients with diabetes were treated with insulin (85.2% [70.9–99.5] at diabetes onset, and 90.5% [81.2–99.7] at follow-up). However, compared to patients with T1DM, significantly more patients in the CHI group with diabetes were treated with conventional insulin therapy (47.8% vs. 24.4%, p?=?0.03 at diabetes onset, and 21.1% vs. 6.4% at follow-up, p?=?0.003), and only a small number of CHI patients were treated with insulin pumps. Daily insulin dose was significantly lower in CHI patients with diabetes than in patients with T1DM, both at diabetes onset (0.3 [0.2–0.5] vs. 0.6?IE/kg/d [0.4–0.8], p?=?0.003) and follow-up (0.8 [0.4–1.0] vs. 0.9 [0.7–1.0] IE/kg/d, p?=?0.02), while daily carbohydrate intake was comparable in both groups. Within the first treatment year, HbA1c levels were significantly lower in CHI patients with diabetes (6.2% [5.5–7.9] vs. 7.2% [6.5–8.2], p?=?0.003), but increased to a level comparable to that of T1DM patients at follow-up. Interestingly, in CHI patients, the risk of severe hypoglycaemia tends to be higher only at diabetes onset (14.8% vs. 5.8%, p?=?0.1).

Conclusions

In surgically treated CHI patients insulin treatment needs to be intensified in order to achieve good glycaemic control. Our data furthermore emphasize the need for improved medical treatment options for patients with diazoxide- and/or octreotide-unresponsive CHI.

     

慢性阻塞性肺疾病合并糖尿病患者肺部真菌感染病原学及易感因素分析

目的探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者肺部真菌感染的病原学及易感因素。方法对58例COPD合并糖尿病肺部真菌感染患者进行病原学及预后分析,并与无糖尿病的COPD真菌感染患者76例进行比较。结果 2组患者病原菌均以白色念珠菌占首位,研究组真菌发病率高于对照组,预后较对照组更差。抗生素、年龄、糖皮质激素和营养状态等因素对2组患者真菌感染的影响差异无统计学意义。结论白色念珠菌仍是COPD患者肺部真菌感染的主要致病菌。糖尿病增加COPD患者感染真菌的风险,并且加重病情,影响预后。     

Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy

BACKGROUND/AIM: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. METHODS: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. RESULTS: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 +/- 119.5 vs. 350.1 +/- 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 +/- 78.2 vs. 368.2 +/- 122.5 ng/ml, p = 0.03) and in the controls (430.3 +/- 78.2 vs. 350.1 +/- 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 +/- 129.2 vs. 427.2 +/- 113.7 ng/ml and 368.2 +/- 122.5 vs. 350.1 +/- 90.2 ng/ml, respectively). CONCLUSIONS: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.     

Association of resistin gene polymorphisms with insulin resistance in Egyptian obese patients

Background

Obesity associated insulin resistance is a major risk factor for type 2 diabetes mellitus. Resistin is recently reported to provide a link between obesity, insulin resistance and type 2 diabetes mellitus. We aimed to investigate the possible associations of resistin gene (RETN) polymorphisms with obesity, and to detect whether these polymorphisms are associated with glucose intolerance and type 2 diabetes mellitus in obese patients.

Methods

One hundred and forty-five Egyptian obese patients with or without glucose intolerance and 155 unrelated healthy controls were enrolled in this study. Polymorphisms of RETN + 299G>A and RETN –420 C>G gene were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Serum resistin was measured by ELISA.

Results

RETN + 299 AA and RETN − 420 GG genotypes were significantly associated with obesity in Egyptian population. Moreover, the mutant alleles or genotypes of both examined polymorphisms were associated with impaired glucose tolerance and diabetes mellitus compared to normal glucose tolerant obese patients. Furthermore, our results revealed elevated waist/hip ratio, BMI, blood pressure, fasting blood glucose level, HOMA-IR, triglycerides, total cholesterol, resistin level, and decreased HDL cholesterol level in homozygote mutant genotypes carriers of both RETN polymorphisms among obese patients.

Conclusion

Resistin gene polymorphisms may play an important role in pathogenesis and susceptibility to obesity, impaired glucose tolerance, and type 2 diabetes mellitus in Egyptian population.     

Characteristic features of etiology and antibiotic susceptibility of urinary tract infection pathogens in patients with diabetes mellitus]

Patients with diabetes mellitus and urinary tract infection were examined. The structure of the pathogens and their antibiotic susceptibility were investigated. Escherichia coli was shown to be the main pathogen of urinary tract infections in the patients with diabetes mellitus. The highest activity against the E. coli isolates was revealed in amoxycillin/clavulanate (92% of the susceptible strains), the 3rd and 4th generation cephalosporins, carbapenems, amikacin (100%) and fluoroquinolones (96%). At the same time the isolates were resistant to aminopenicillins and co-trimoxazole (29.3 and 16% respectively).     

Anatomic changes in the biliary tract and pancreas in patients with diabetes mellitus diagnosed by endoscopic retrograde cholangiopancreatography]

Structural changes in both biliary tract and pancreas have been assessed with endoscopic retrograde cholangiopancreatography in 100 diabetic patients divided into subgroups depending on the type of diabetes mellitus, i.e. type I, type II and III-pancreatic. Control group included 100 randomly selected patients without diabetes mellitus in whom endoscopic retrograde cholangiopancreatography has been performed for various indications. Structural changes in the biliary tract and pancreas have been more frequent in diabetic patients than in the control group (47 and 75% vs 32 and 30%, respectively). Cholelithiasis has been noted in 27.8% of patients with type II diabetes mellitus and in 11.3% of patients with type I diabetes mellitus; obesity has been found in 57 and 12% of patients, respectively. Other biliary tract disorders, mainly in the form of segmental stenosis or dilatation of the common bile duct, have been more frequent in patients with type II diabetes mellitus. Pancreatic disorders, assessed with the aid of Cambridge classification, have been noted in all patients with pancreatic diabetes and in 80.7% of patients with diabetes mellitus type I. Incidence of so-called doubtful and mild disorders has been more frequent (22.2 and 24.1%, respectively) in patients with diabetes mellitus type II whereas "moderate" and "severe" disorders have been significantly less frequent (7.4 and 1.9% of patients). The results indicate, that endoscopic retrograde cholangiopancreatography is useful in the assessment of bile ducts structure and pancreatic exocrine activity in diabetic patients in whom disorders are more frequent.     

Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells

Oxidative stress plays an important role in the pathogenesis of insulin resistance and type 2 diabetes mellitus and in diabetic vascular complications. Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, improve insulin sensitivity and are currently used for the treatment of type 2 diabetes mellitus. Here, we show that TZD prevents oxidative stress-induced insulin resistance in human skeletal muscle cells, as indicated by the increase in insulin-stimulated glucose uptake and insulin signaling. Importantly, TZD-mediated activation of PPARgamma induces gene expression of glutathione peroxidase 3 (GPx3), which reduces extracellular H(2)O(2) levels causing insulin resistance in skeletal muscle cells. Inhibition of GPx3 expression prevents the antioxidant effects of TZDs on insulin action in oxidative stress-induced insulin-resistant cells, suggesting that GPx3 is required for the regulation of PPARgamma-mediated antioxidant effects. Furthermore, reduced plasma GPx3 levels were found in patients with type 2 diabetes mellitus and in db/db/DIO mice. Collectively, these results suggest that the antioxidant effect of PPARgamma is exclusively mediated by GPx3 and further imply that GPx3 may be a therapeutic target for insulin resistance and diabetes mellitus.     

Factors predicting the course of diabetes mellitus in hyperthyroid patients

The relationship between changes in glucose tolerance with treatment of hyperthyroidism and various factors that might be relevant to carbohydrate metabolism were investigated in 64 hyperthyroid patients with abnormal glucose tolerance, including 35 cases with fasting plasma glucose (FPG) levels of 140 mg/dl or more. All patients had diffuse toxic goiter. After correction of the hyperthyroidism, glucose intolerance improved in almost all cases, even in cases with fasting hyperglycemia, but diabetes mellitus in patients with FPG above 140 mg/dl and/or delta IRI/delta PG X 30' during a 50-g oral glucose tolerance test below 0.10, persisted. Patients who showed diabetic glucose tolerance even after remission from thyroid dysfunction had significantly lower delta IRI/delta PG X 30' values and a higher incidence of family histories of diabetes mellitus than those not showing diabetic glucose tolerance. There were no significant differences in serum T3 and T4 levels between these two groups of patients. The findings suggest that predisposition to diabetes may be an important factor in persistent glucose intolerance in the hyperthyroidism of Graves' disease. The FPG and delta IRI/delta PG X 30' values may be useful in predicting which patients with hyperthyroidism will have permanent diabetes.     

Antithrombin III and alpha-2-antiplasmin activities compared with other hemostasis parameters in uncomplicated diabetes mellitus, type 2]

In 40 patients with diabetes mellitus type II without clinical signs of any organ complications and in the respective control group the following indices of hemostasis were assessed: 1) activity of AI-III, 2) activity of alfa-2-AP, 3) fibrinogen, 4) time of fibrinolysis, 5) platelets count, adhesiveness and spontaneous aggregation, 6) kaolin-cephalin and profil stipven-cephalin plasma times. All these indices were normal in uncomplicated diabetes mellitus with the expectation of platelets activity. Stimulation of platelets activity and increase of corresponding parameters appears in diabetes mellitus type II before any other symptoms of angiopathy.