Does autoimmune hypothyroidism increase the risk of neurovascular complications in type 1 diabetes?

BACKGROUND: Type 1 diabetes (T1DM) often coexists with other autoimmune diseases, most commonly with hypothyroidism. To date, the influence of coexisting autoimmune hypothyroidism (AHT) on the course of chronic neurovascular complications of autoimmune diabetes has not been established. The aim of the study was to assess the relationship between AHT and the occurrence of chronic T1DM complications. METHODS: The study group comprised 332 European Caucasian participants with T1DM [165 (49.7%) men]. AHT was recognized in subclinical and overt hypothyroidism and confirmed by the presence of anti-thyroid autoantibodies: anti-peroxidase (ATPO) and/or anti-thyroglobulin (ATg) and ultrasonography (hypoechogenicity, parenchymal heterogeneity, lymph nodes assessment). RESULTS: In the analyzed group, 48.5% of patients were diagnosed with at least one neurovascular complication. At the time of enrollment, 16.3% of participants were diagnosed with AHT. Patients with AHT, compared to those without AHT, were characterized by a higher prevalence of neurovascular complications (64.8 vs. 45.3%; P = 0.009) and retinopathy (55.6 vs. 38.9%; P = 0.02). There were significant differences between groups with and without neurovascular complications, with regard to classic risk factors for chronic diabetes complications: age, T1DM duration, SBP, DBP, HbA1c, TG, eGFR and hypertension prevalence. In the multivariate logistic regression analysis, AHT was an independent predictor of neurovascular complications after adjusting for age, DBP, HbA1c and TG (odds ratio, 2.40; 95% confidence interval, 1.17-4.92; P = 0.02). CONCLUSIONS: AHT coexisting with T1DM was associated with a higher incidence of neurovascular complications.

Accumulation of advanced glycation end products in the skin is accelerated in relation to insulin resistance in people with Type 1 diabetes mellitus.

AIM: To evaluate the association between skin advanced glycation end products and insulin resistance in Type 1 diabetes. METHODS: The study group consisted of 476 people with Type 1 diabetes (247 men) with a median (interquartile range) age of 42 (33-53) years, disease duration of 24 (19-32) years and HbA1c concentration of 63 (55-74) mmol/mol [7.9 (7.2-8.9)%]. Insulin resistance was assessed according to estimated glucose disposal rate. Advanced glycation product accumulation in the skin was measured by autofluorescence using an AGE Reader. The group was divided into three subgroups based on estimated glucose disposal rate tertiles (<5.5, 5.5-9.5 and >9.5 mg/kg/min, respectively). The higher the estimated glucose disposal rate, the lower the insulin resistance. RESULTS: Skin autofluoresence level decreased with increasing estimated glucose disposal rate; comparing people below the lower tertile, with those between the first and third tertiles, and with those above the third tertile, the median autofluoresences were, respectively: 2.5 (2.2-2.9) vs 2.3 (2.0-2.7) vs 2.1 (1.9-2.5) AU (P<0.0001). A negative correlation was observed between skin autofluorescence and estimated glucose disposal rate (Spearman's correlation coefficient=-0.31, P <0.001). Multiple logistic regression showed a significant, two-way association of insulin resistance with skin autofluorescence. CONCLUSION: The results of this study offer strong evidence for a two-way relationship between insulin resistance and advanced glycation product accumulation in the skin in people with Type 1 diabetes.

The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration.

AIM: The aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). METHODS: We evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33-53) years, disease duration of 25 (IQR: 20-32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. RESULTS: Patients with abnormal ESC had higher skin AF [2.5 (2.1-2.9) vs 2.1 (1.9-2.5) AU, p < 0.001], lower eGFR [83 (72-96) vs 98 (86-108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12-81) vs 14 (7-43) PU, p < 0.001], lower THmax [664 (137-1461) vs 1115 (346-1933) %, p = 0.002], higher PORHpeak [104 (59-167) vs 70 (48-135) PU, p < 0.001] as compared to subjects with normal ESC results. We found negative correlation between THmax and TG level (Rs = -0.14, p < 0.005), AF (Rs = -0.19, p = 0.001), vibration perception threshold - VPT (Rs = -0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = -0.2, p < 0.001), HDL (Rs = -0.12, p = 0.01), Feet ESC (Rs = -0.27, p < 0.001) and Hand ESC (Rs = -0.16, p = 0.002). CONCLUSION: Impaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.

Does serum cystatin C level reflect insulin resistance in patients with type 1 diabetes?

OBJECTIVES: The aim of study was to evaluate the relationship between serum cystatin C and insulin resistance (IR) in type 1 diabetic patients being the participants of Poznan Prospective Study. DESIGN AND METHODS: The study was performed on 71 Caucasian patients (46 men); with type 1 diabetes, who were recruited into the Poznan Prospective Study, at the age of 39±6.1 meanly, and treated with intensive insulin therapy since the onset of the disease. The follow-up period and diabetes duration were 15±1.6 years. Insulin resistance (IR) was assessed by estimated glucose disposal rate (eGDR) calculation with cut-off point 7.5 mg/kg/min. Patients were divided into two groups, according to the presence or absence of IR. RESULTS: From among 71 patients, 31 patients (43.7%) presented decreased sensitive to insulin with eGDR below 7.5 mg/kg/min. Patients who had eGDR <7.5 mg/kg/min (insulin resistant), compared with subjects with eGDR >7.5 mg/kg/min (insulin sensitive), had higher level of serum cystatin C [0.59 (IQR:0.44-0.84) vs 0.46 (IQR:0.37-0.55) mg/L, p=0.009]. A significant negative correlation between cystatin C and eGDR was revealed (Rs=-0.39, p=0.001). In regression model cystatin C was related to insulin resistance, adjusted for sex, BMI, eGFR and duration of diabetes [OR 0.03 (0.001-0.56), p=0.01]. CONCLUSIONS: Higher level of serum cystatin C is related to decreased insulin sensitivity in patients with type 1 diabetes. This relationship seems to have an important clinical implication.

Lower melanin content in the skin of type 1 diabetic patients and the risk of microangiopathy.

BACKGROUND: Various skin diseases are commonly observed in diabetic patients. Typical biophysical properties of diabetic skin such as lower skin elasticity, decreased water content in stratum corneum, increased itching and sweating disturbances are reported. The aim of the study was to examine the distribution and intensity of skin pigmentation in diabetic patients in correlation with the metabolic control and with presence of microangiopathy. MATERIAL AND METHODS: The study was conducted on 105 patients (42 men and 63 women, median age 31), with type 1 diabetes (DM1). The control group of 53 healthy individuals (22 men and 31 women) was age- and sex-matched. Skin pigmentation was measured at 3 different locations of the body (cheek, dorsal surface of a forearm and dorsal surface of a foot) using Mexameter® MX 18. We calculated melanin index (MI) by the meter from the intensities of absorbed and reflected light at 880 nm. RESULTS: Patients with DM1 had lower MI on the foot (173.2 ± 38.8 vs. 193.4 ± 52.7, p=0.016) as compared to controls. In the univariate analysis cheek MI was negatively related to HbA1c level (ß=-4.53, p=0.01). Forearm MI was negatively associated with daily insulin dose (ß=-0.58, p=0.01), BMI (ß=-3.02, p<0.001), waist circumference (ß=-0.75, p=0.009), serum TG concentration (ß=-18.47, p<0.001) and positively with HDL cholesterol level (ß=15.76, p=0.02). Diabetic patients with hypertension had lower foot MI values (ß=-18.28, p=0.03). Lower MI was associated with the presence of diabetic neuropathy (ß=-18.67, p=0.04) and retinopathy (ß=-17.47, p=0.03). CONCLUSIONS: In conclusion, there seems to be loss of melanocytes in type 1 diabetes. The melanin content is related to glycemic control of diabetes and obesity. The lower melanin content the higher possibility of microangiopathy. This is a first report in the literature devoted to distribution of melanin in the skin of type 1 diabetic patients.

Higher risk of microvascular complications in smokers with type 1 diabetes despite intensive insulin therapy.

AIM: The aim of the study was to evaluate the relationship between smoking status and the incidence of microvascular complications in patients with type 1 diabetes (DM1), treated with intensive functional insulin therapy (IFIT) from the onset of the disease. METHODS: 81 participants (51 men, 30 women) of Poznan Prospective Study (PoProStu) with mean age of 34.0 ± 6.4 years were included in this analysis. Patients were observed for 10.0 ± 1.5 years. Evaluation of microvascular complications of diabetes, such as retinopathy, diabetic kidney disease and neuropathy was performed. Patients were divided into two groups depending on the smoking status: smokers and non-smokers. RESULTS: In the group of smokers (n=36) in comparison with patients who had never smoked (n=45) any microangiopathy (58.3% vs 33.3%, p=0.02), retinopathy (44.4% vs 20%, p=0.02), diabetic kidney disease (47.2% vs 24.4%, p=0.03) and neuropathy (25% vs 4.4%, p=0.02) were found more often. A significant relationship, adjusted for age, sex, duration of diabetes, presence of hypertension and HbA1c between smoking and neuropathy and retinopathy was revealed [OR 10.16 (95%CI 1.59-64.95); p=0.01 and OR 3.50 (95%CI 1.01-12.12); p=0.04, respectively]. CONCLUSION: The results show that in patients with DM1, there is a strong relationship between smoking and the diabetic microvascular complications, especially with neuropathy, despite treatment from the initial diagnosis with intensive insulin therapy.

Does glucagon stimulation test help to predict autoimmunity in newly diagnosed non obese adults with diabetes?

Classification of diabetes type in adults patients remains difficult. This study was undertaken to determine the relationship between presence of autoantibodies in the serum and the result of glucagon stimulation test in non obese patients at aged above 35 years with newly diagnosed diabetes.Study involved 52 non obese adults aged 42 years [interquartile range (IQR): 37-46], with body mass index (BMI) 23.7 kg/m2 (IQR: 21.4-26.2). Presence of autoantibodies to islet cells (ICA), antibodies to tyrosine phosphatase (IA-2), glutamic acid decarboxylase autoantibodies (anti-GAD) and plasma fasting and stimulating (6 min after intravenous injection of 1 mg glucagon) C-peptide level was assessed.73.1% subjects had at least 1 of 3 assessed autoantibodies, 26.9% patients were autoantibodies negative. According to serum C-peptide concentration after stimulation test with glucagon patients were divided into 2 groups. Receiver Operating Characteristic (ROC) Curve for determination of an optimal cut-point (C-peptide stimulation above and below 1.6) was used. In patients with negative stimulation test higher prevalence of 2 (33.3% vs. 66.7%; p=0.04) or 3 (12.5% vs. 87.5%, p=0.01) positive autoantibodies was noticed in comparison to patients with positive stimulation test. Multivariate logistic regression showed that presence of autoantibodies was independently associated with stimulated C-peptide level (OR 2.3; 95%CI: 1.07-5.28, p=0.03).Autoimmune diabetes should be suspected in subjects with lower response of ß- cell in glucagon stimulation test. If the C-peptide do not increase more than 1.6 after glucagon presence of autoanibodies is more probable.

Smoking and other factors associated with short-term partial remission of Type 1 diabetes in adults.

AIMS: The duration of partial remission of Type 1 diabetes is associated with the degree of initial metabolic disturbance and features of insulin resistance. Cigarette smoking decreases insulin sensitivity, but its influence on the length of remission is unknown. Therefore, this study assessed the relationship between cigarette smoking and duration of partial remission in adults with newly diagnosed Type 1 diabetes. METHODS: We recruited 149 patients (48 women and 101 men, aged 16-35 years, median age 25 years), admitted to a teaching hospital with newly diagnosed Type 1 diabetes and followed them for a median period of 1 year and 9 months. We introduced intensive insulin therapy in multiple injections (basal-bolus) in all patients. We defined partial remission as an insulin dose of ≤ 0.3 U/kg body weight/24 h, an HbA(1c) value < 53 mmol/mol (7.0%) and a random serum C-peptide concentration over 0.5 ng/ml. Cigarette smoking was determined by self-report. RESULTS: Of 149 patients, 68 (46%) fulfilled the criteria for partial remission at 1 year after diagnosis of diabetes. Fewer patients who were in partial remission at 1 year smoked (19/68, 28%) than did patients that were not in partial remission (41/81, 51%). In logistic regression analyses, non-smoking was associated with remission at 1 year independent of age, sex, HbA(1c) and presence of diabetic ketoacidosis, all measured at onset of diabetes (OR 3.32, 95% CI 1.42-7.75, P = 0.005). CONCLUSION: Relative to individuals in this study who smoked, those who did not smoke at diagnosis of Type 1 diabetes experienced a longer duration of partial remission.

Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients are dependent on age and mean blood pressure.

AIM: The aim of the study was to assess the factors that influence carotid intima-media thickness (CIMT) and arterial stiffness in type 1 diabetic patients. MATERIAL AND METHODS: We included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years, disease duration 10 years, HbA1c 8.2%. CIMT was measured using high resolution ultrasonography. Arterial stiffness was assessed with the use of digital volume pulse analysis and tonometric measurement of wave reflection and central haemodynamics. Serum C-reactive protein (hsCRP), matrix metalloproteinase-9 (MMP-9), soluble intracellular adhesion molecule-1 (sICAM-1) and myeloperoxidase (MPO) concentrations were also measured. RESULTS: CIMT and arterial stiffness correlated with age, duration of diabetes, systolic and diastolic blood pressure, GFR-glomerular filtration rate and sICAM-1. Multiple regression analysis identified only age as significant determinant of CIMT. Age, mean blood pressure and GFR, but not duration of diabetes were significant determinants of arterial stiffness. CONCLUSIONS: In type 1 diabetic patients both CIMT and arterial stiffness were related to age, blood pressure, kidney function and sICAM-1 serum concentration.

Insulin resistance is associated with microangiopathy in type 1 diabetic patients treated with intensive insulin therapy from the onset of disease.

AIM: The aim of the study was to evaluate the relationship between indirect parameters of insulin resistance (IR) and risk of microangiopathy in patients with type 1 diabetes (DM1), treated from the initial diagnosis with intensive insulin therapy. METHODS: The study group consisted of 81 patients with DM1 (51 men, 30 women), aged 34±6.4, and who were observed for 10±1.5 years. Indirect parameters of IR were evaluated: waist circumference, waist to hip ratio (WHR), body mass index (BMI), daily insulin requirement, gain of weight from the beginning of the disease, lipid profile, estimated glucose disposal rate (eGDR), inflammatory markers and features of metabolic syndrome. Patients were divided into two groups depending on the presence or absence of microangiopathy. RESULTS: In the group with microangiopathy (n=36) in comparison with patients without complications (n=45) we found: larger waist circumference (88.9±11.7 vs. 83.7±10.2 cm; p=0.036), higher weight before diabetes (77.3±17.0 vs. 67.0±12.5 kg; p=0.008), higher WHR (0.90±0.08 vs. 0.86±0.08; p=0.048), higher level of triglycerides (1.3±0.8 vs. 0.9±0.3 mmol/l; p=0.002) and lower eGDR (7.2±2.4 vs. 8.8±1.9 mg/kg/min; p=0.0019). In patients with microangiopathy, features of metabolic syndrome were found more often (12 (33.3%) vs. 4 (8.9%); p=0.006). A significant relationship, adjusted for sex, age and duration of diabetes, between eGDR and microangiopathy was revealed (OR 0.65 (95%CI 0.49-0.86); p=0.0037). CONCLUSION: The results show that in patients with DM1, treated from the initial diagnosis with intensive insulin therapy, there is an independent relationship between IR and the diabetic microangiopathy.