THE IMPACT OF HYPOGLYCEMIA AND EPA AND DHA SUPPLEMENTATION ON BRAIN-DERIVED NEUROTROPHIC FACTOR LEVEL IN PREGNANT WOMEN WITH TYPE 1 DIABETES: A PROSPECTIVE COHORT STUDY

Background: In addition to its neuroprotective effect, Brain-derived neurotrophic factor (BDNF) also plays a role in glucose and lipid metabolism. This study aims: a) to find changes in the BDNF concentration during pregnancy in type 1 diabetes. b) to prove the effect of DHA and EPA supplementation on changes in BDNF concentrations c) to investigate the impact of hypoglycemia on BDNF concentration. Subjects and methods: The data from this study were from the PRE-HYPO cohort study. Twenty-one of them were on a standard diabetic diet enriched with EPA and DHA (EPA 120 mg/day and DHA 616 mg/day; Exposed group), and nineteen pregnant diabetic women were on the standard diabetic diet without EPA and DHA supplementation (Non-exposed group). In the first trimester of pregnancy, fift .9 mmol/L; HYPO+ group), and twenty-five pregnant women did not have hypoglycemia episodes (HYPO- group). Results: BDNF concentration significantly decreased during pregnancy from the first to the third trimester, in Non-exposed from 25.1 (22.0-30.2) to 22.1 (16.3-28.2), P<0.05, in the Exposed group from 22.1 (19.8-25.9) to 18.1 (14.8-18.9), P<0.01. Pregnant patients with hypoglycemia episodes (HYPO+ subgroup) had significantly higher BDNF in the third trimester of pregnancy [22.5 (20.6-28.4)] when compared with patients who did not develop hypoglycemia [16.3 (14.3-18.8), P<0.001]. In the third trimester of pregnancy, BDNF and n-6 PUFAs were associated with hypoglycemia (OR 1.818 95 % CI 1.079-3.003, P=0.025; OR 1.103 95 % CI 1.001-1.217, P=0.048). Total F.A.s were inversely associated with hypoglycemia (OR 0.969 95% CI 0.939-0.998, P=0.048). Conclusion: Pregnant women with hypoglycemia (HYPO+ group) had higher concentrations of BDNF in the first and third trimesters of pregnancy compared to those without hypoglycemia. An increase in body weight during pregnancy leads to a decrease in BDNF concentration

Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus

AIMS: To determine whether cardiac autonomic dysfunction represents a risk factor for diabetic retinopathy (DR) development and progression in persons with type 1 diabetes mellitus (T1DM). ----- METHODS: The study comprised 154 normoalbuminuric persons with T1DM divided into two groups according to the DR presence: with and without DR. Cardiovascular autonomic functioning was measured at baseline using conventional and spectral analysis. Participants were re-examined for the DR presence 18months after. ----- RESULTS: The group with DR had longer disease duration compared to the group without DR (20 vrs 11.5years, p<0.001), heart rate coefficient of variation (HRV-CV) at rest and during deep breathing were lower in participants with DR (p=0.001 and 0.004), as well did spectral indices of HRV: low frequency (LF) band, high frequency (HF) band (p=0.003 and 0.022) while LF/HF ratio indicating sympathovagal balance was higher (p=0.037). No difference in glycaemic control or blood pressure value were observed. Twenty-one (13.36%) participants developed non proliferative DR or progressed to proliferative DR. Cox proportional regression showed that the 18months risk from retinal deterioration was reduced by 33.4% by each increase in the HRV-CV of 1%, 12.7% for the same HRV-CV increase during deep breathing while LF band of 1ms(2) results in 8.6% risk reduction. ----- CONCLUSIONS: This study provides evidence that DR should not be considered merely a metabolic control manifestation and that HRV-CV as well as spectral indices of HRV might serve as a practical tool to identify a subgroup of T1DM patients with higher risk of retinal deterioration

Positive Association between Preserved C-Peptide and Cognitive Function in Pregnant Women with Type-1 Diabetes

This study focused on the cognitive function of women with type 1 diabetes in pregnancy. We investigated risk factors for a low cognitive score such as age, duration of Diabetes, BMI, subclinical hypothyroidism, cardiovascular autonomic neuropathy, the impact of hypo-/hyperglycemia, and C-peptide preservation. Material and methods. Seventy-eight pregnant women with type 1 diabetes (age 31.1 ± 5.4 years, diabetes duration 14.3 ± 8.9 years) were included in the study. Cognitive function was assessed in different domains, such as reasoning, memory, attention, coordination, and perception. Results. The cognitive test values ≥400 were considered high scores, and values 25 kg/m2 2.208 (95% CI 1.116–4.370), HbA1c > 6.5% RR 0.774 (95% CI 0.366–1.638), subclinical hypothyroidism RR 3.111 (95% CI 1.140–8.491), and impaired cardiovascular autonomic neuropathy RR 2.250 (95% CI 1.000–5.062). Pregnant women with a lower score for general cognitive function had higher BMI and higher leptin levels. Preserved C-peptide reduces the risk for cognitive impairment (RR 0.297 (95% CI 0.097–0.912)) in pregnant women with type 1 diabetes Conclusion. BMI > 25 kg/m2, subclinical hypothyroidism, and cardiovascular autonomic neuropathy are associated with increased risk, and postprandial C-peptide preservation with reduced risk for cognitive impairment in pregnant women with type 1 diabetes

Preserved C-peptide secretion in patients with type 1 diabetes and incipient chronic complications is associated with lower serum resistin and higher uric acid levels

Background and aims: Previous studies suggested that long-term perseverance of beta-cell function in patients with type 1 diabetes (T1DM) is associated with lower incidence of microvascular complications. The objective of this study was to evaluate preserved C-peptide secretion in patients with T1DM without overt chronic complications and to explore associations with resistin and uric acid as biomarkers of microvascular complication pathogenesis. ----- Materials and methods: We assessed residual beta-cell function in 164 T1DM patients (male/female = 91/73; age/diabetes duration range = 18-70/1-30 years) using an ultrasensitive C-peptide ELISA assay with detection limit of 2.5 pmol/L and total coefficient of variation (CV) 5,8% (Mercodia, Sweden). Serum level of uric acid was measured by enzymatic method (AU680, Beckman Coulter, USA) while resistin concentration was determined by the ELISA assay (Biovendor, Czech Republic). ----- Results: C-peptide secretors had shorter diabetes duration (5.1 vs. 16 years; p < 0,001), lower resistin (4.53 vs. 4.93 mg/mL p = 0.045), and higher uric acid (259 vs 238 μmol/L, p = 0.048) level than T1DM patients with no detectable C-peptide levels, while no differences in routine anthropometric and laboratory variables, including HbA1c, were observed. Although the proportion of C-peptide secretors significantly decreased across categories of diabetes duration (70%, 38%, 17% and 15% for <5, 5-10, 10-20 and 20-30 years of duration, respectively; p < 0,001), detectable C-peptide was found in 5/23 T1DM patients who were diagnosed with T1DM more than 20 years ago. ----- Conclusion: The results of our study revealed that patients with detectable C-peptide had lower resistin and higher uric acid level compared to patients with undetectable C-peptide

Relationship between β-Cell Autoantibodies and Their Combination with Anthropometric and Metabolic Components and Microvascular Complications in Latent Autoimmune Diabetes in Adults

Aims: Our study aimed to investigate the relationship between three autoantibodies and their combination with anthropometric and metabolic components and microvascular complications in patients with latent autoimmune diabetes in adults (LADA). Methods: Our study included 189 LADA patients divided into four subgroups according to the autoantibodies present: glutamic acid decarboxylase autoantibodies (GADA) only; zinc transporter-8 autoantibodies (ZnT8A)+GADA; insulinoma-associated-2 autoantibodies (IA-2)+GADA; and ZnT8+IA-2+GADA. Results: Compared to GADA positivity only, patients with ZnT8+GADA positivity and ZnT8+IA-2+GADA positivity had a shorter diabetes duration and lower body mass index (BMI); patients with ZnT8+GADA positivity were younger and showed an increase in glomerular filtration rate, while those with ZnT8+IA-2+GADA positivity had lower C-peptide and lower insulin resistance measured with HOMA2-IR. In a multiple regression analysis, ZnT8 positivity was associated with lower BMI (p = 0.0024), female sex (p = 0.0005), and shorter duration of disease (p = 0.0034), while IA-2 positivity was associated with lower C-peptide levels (p = 0.0034) and shorter diabetes duration (p = 0.02). No association between antibody positivity and microvascular complications of diabetes, including retinopathy, neuropathy, and microalbuminuria, as well as with variables of glucose control and β-cell function were found. Conclusion: The results of our study suggest that ZnT8 and IA-2 autoantibodies are present in a significant number of LADA patients and associated with clinical and metabolic characteristics resembling classic type 1 diabetes. Due to increased LADA prevalence, earlier identification of patients requiring frequent monitoring with the earlier intensification of insulin therapy might be of special clinical interest

Serum adipocytokines are associated with microalbuminuria in patients with type 1 diabetes and incipient chronic complications

Recent studies have implicated possible contribution of adipocytokines in development and progression of microvascular complications in patients with type 1 diabetes (T1DM). The aim of our study was to investigate relationship between adipocytokines, namely leptin, resistin, adiponectin and dipeptidyl peptidase-4 (DPP-4) activity, with albuminuria in T1DM. This study included 202 T1DM without or with incipient microvascular complications. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. Serum DPP-4 activity was measured by a colorimetric assay procured, and the level of adiponectin, leptin, and resistin was determined by the ELISA method. Serum DPP-4 activity and adiponectin was significantly higher in patients with normoalbuminuria compared to patients with microalbuminuria (47 vs 36 U/L, and 10.9 vs 7.3 ug/mL, respectively, p≤0.02). In multivariate logistic regression analysis adiponectin and serum DPP-4 activity was significantly associated with risk of microalbuminuria in our subjects (p≤0.04), with odds ratios of 0.72 to 0.99. However, after adjustment for age, sex, HbA1c, duration of diabetes and BMI, only serum DPP-4 activity was significantly associated with risk of microalbuminuria (p=0.008). The results of our study suggest that serum DPP-4 activity is lower in T1DM with microalbuminuria. Prospective studies are warranted to evaluate the relationship between serum DPP-4 activity and progression and development of albuminuria and nephropathy in T1DM

N-glycosylation of serum proteins in adult type 1 diabetes mellitus exposes further changes compared to children at the disease onset

Objective: Previously we have shown that plasma protein N-glycosylation is changed in children at the onset of type 1 diabetes. In this study, we aim to identify N-glycan changes in adults with T1DM, compare them to those in children, and investigate their associations with disease duration, complications, glycaemic status, and smoking. Methods: Serum protein N-glycans from 200 adults with type 1 diabetes and 298 healthy controls were analysed using ultra-high performance liquid chromatography and divided into 39 directly measured glycan groups from which 16 derived traits were calculated. Results: Compared to healthy controls, subjects with type 1 diabetes showed differences in 19 glycan groups and a decrease in monogalactosylated, an increase in digalactosylated, monosialylated, and antennary fucosylated derived traits, from which changes in monogalactosylation and seven directly measured traits overlapped with previously reported in children. Changes in four directly measured and two derived traits previously seen in children were not detected in adults. HbA1c was positively associated with sialylated and highly branched structures, whereas N-glycome was not influenced by disease duration or diabetic complications. Conclusions: Our results suggest potential N-glycome involvement in different stages of type 1 diabetes, including processes underlying its development, the disease itself, as well as those occurring after disease establishment

Human complement component C3 N-glycome changes in type 1 diabetes complications

Aim: Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. Research design and methods: Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. Results: Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. Conclusion: This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity