Flash Glucose Monitoring in Croatia: The Optimal Number of Scans per Day to Achieve Good Glycemic Control in Type 1 Diabetes.

Background and Objectives: The purpose of this study is to determine the optimal number of scans per day required for attaining good glycemic regulation. Materials and Methods: The association of scanning frequency and glucometrics was analyzed according to bins of scanning frequency and bins of time in range (TIR) in the Croatian population of type 1 diabetes (T1DM) patients. Results: Intermittently scanned continuous glucose monitoring (isCGM) Libre users in Croatia performed on average 13 ± 7.4 scans per day. According to bins of scanning frequency, bin 5 with 11.2 ± 02 daily scans was sufficient for achieving meaningful improvements in glycemic regulation, while decreasing severe hypoglycemia required an increasing number of scans up to bin 10 (31 ± 0.9), yet with no effect on TIR improvement. When data were analyzed according to bins of TIR, an average of 16.3 ± 10.5 scans daily was associated with a TIR of 94.09 ± 3.49% and a coefficient of variation (CV) of 22.97 ± 4.94%. Improvement was shown between each successive bin of TIR but, of notice, the number of scans performed per day was 16.3 ± 10.5 according to TIR-based analysis and 31.9 ± 13.5 in bin 10 according to scan frequency analysis. Conclusions: In conclusion, an optimal average number of scans per day is 16.3 in order to achieve glucose stability and to minimize the burden associated with over-scanning.

The Association of Personality Traits and Parameters of Glycemic Regulation in Type 1 Diabetes Mellitus Patients Using isCGM.

This study aimed to examine the impact of personality on glycemic regulation in adult patients with type 1 diabetes mellitus (T1DM). The study group consisted of subjects with T1DM, who were ≥ 18 years of age. The study was conducted in two phases: At baseline, subjects completed the Croatian version of the International Personality Item Pool scale (IPIP50s) and a questionnaire designed to gather socioeconomic data, duration of diabetes, presence of chronic complications, presence of cardiovascular risk factors, frequency, and type of pre-existing hypoglycemic episodes per week. Blood and urine samples were collected and body mass index (BMI) was calculated. Each participant was provided with the intermittently scanned glucose monitoring system (isCGM) Freestyle Libre. During the second visit (3 months from the start of the trial), glycemic parameters were collected from the reports generated from the Freestyle Libre system. Estimated glycated hemoglobin (HbA1c) values were significantly lower after three months compared to baseline HbA1c (Wilcoxon test, p < 0.001). An inverse correlation between the number of daily scans and degree of extraversion among subjects was observed, e.g., higher degrees of extraversion resulted in lower numbers of daily scans, while lower degrees of extraversion, i.e., introvertedness, resulted in higher numbers of daily scans (Rho = −0.238 p = 0.009). There was a positive correlation between emotional stability and time spent in hypoglycemia (Rho = 0.214; p = 0.02). In addition, a shorter duration of diabetes was associated with higher percentages of TIR and vice versa (p = 0.02). Investigating personality traits can be a useful tool for identifying patients predisposed to hypoglycemia and lower scanning frequency. Patients with a longer history of T1DM require closer follow-up and should be re-educated when necessary.

Association Between Interleukin-10 Gene (-1082g/A) Polymorphism and Type 2 Diabetes, Diabetes-Related Traits, and Microvascular Complications in the Croatian Population.

Interleukin (IL)-10 is an anti-inflammatory cytokine, and a decrease in its secretion is associated with obesity, metabolic syndrome and type 2 diabetes. However, it has not been established whether the intensity of the immune response during diabetes-associated chronic inflammation affects the development and/or progression of type 2 diabetes and its microvascular complications. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP)-1082G/A for IL-10 gene in development of diabetes type 2 and its complications. DNA was extracted from blood cells of 240 overweight/obese subjects for IL-10 genotyping. Based on the presence of diabetes type 2, patients were divided in two groups: experimental group of 144 patients with diabetes type 2 and control group of 96 age- and gender-matched subjects without diabetes. Compared to control group, diabetic group had higher levels of leukocytes (p=0.012), fibrinogen (p=0.049) and plasminogen activator inhibitor-1 (PAI-1) (p=0.009), and lower levels of albumin (p=0.001). There were no differences in the frequency of SNP-1082G/A for IL-10 gene between the two groups (p=0.654). When considering diabetes related traits in all subjects in relation to specific genotype, a group with homozygous (AA) genotype had higher values of the mean fasting glucose (p<0.000001), HbA1c (p<0.000001) and HOMA-IR (p=0.003632), while the mean HOMA-B value (p=0.000178) was lower when compared to the groups with GG and GA genotypes. There was no difference in devel-opment of diabetic nephropathy, retinopathy and polyneuropathy between the IL-10 polymorphism genotypes. In conclusion, obese diabetes type 2 patients had an increased inflammation activity com-pared to obese non-diabetic individuals. There was no association of the investigated polymorphisms and development of type 2 diabetes and its microvascular complications. However, diabetes related traits clearly depended on the presence of specific IL-10 genotype.

Plasminogen activator inhibitor-1 concentrations and bone mineral density in postmenopausal women with type 2 diabetes mellitus.

BACKGROUND: Women with type 2 diabetes mellitus (T2DM) have a higher risk of fractures despite increased bone mineral density (BMD). In experimental studies a potential role of plasminogen activator inhibitor-1 (PAI-1) in bone remodeling is suggested but studies in humans are lacking. This is a first study in humans investigating whether circulated levels of PAI-1 in postmenopausal women with T2DM are related to BMD and adiposity. METHODS: Anthropometric variables, PAI-1 and insulin levels, serum lipids and bone turnover markers were measured in 127 postmenopausal women with T2DM. A total of 117 female patients were divided according to lumbar spine BMD measurements via dual-energy x-ray absorptiometry in three groups: 47 with osteopenia, 21 with osteoporosis and 49 with normal BMD. RESULTS: Diabetic patients with normal BMD had significantly higher BMI, greater waist circumference and lower bone turnover markers than diabetics with osteopenia and osteoporosis. PAI-1 was lower in diabetics with osteoporosis and osteopenia compared with diabetics with normal BMD. Multiple regression analysis revealed insulin, triglycerides levels, pyrilinks and beta blocker therapy to be the strongest predictors of PAI-1 levels. PAI-1 levels correlated with both L-BMD and hip BMD, but after adjustment for age and BMI association was no longer significant. CONCLUSION: Our findings suggest that elevated PAI-1 levels are associated with higher BMD in obese diabetic patients but the possible implications of this finding and underlying mechanisms still remain unclear. Obviously, metabolic parameters, may affect both BMD and PAI-levels, and association of PAI-1 and BMD could be indirect. However, as pyrilinks is also independently and significantly negatively correlated to PAI-1 its direct involvement in bone metabolism is also plausible. Further investigations are needed to elucidate the nature of interaction of this matrix modulator in relation to energy and bone metabolism in humans.

Hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with type 2 diabetes and relations with insulin resistance and chronic complications.

OBJECTIVE: Connection between abdominal obesity, type 2 diabetes, and the hypothalamic-pituitary-adrenal (HPA) axis activity remains unclear. The aim of this study was to measure HPA axis activity in 121 type 2 diabetics, in 29 obese subjects, and 19 control subjects. RESEARCH DESIGN AND METHODS: Physical examination, anthropometric measures, psychological questionnaire, psychiatric interview, neurological and ophthalmologic examination were performed. Biochemical parameters, urinary free cortisol levels (UFC), cortisol and ACTH levels at 8 and 16 h, cortisol levels after overnight suppression with 1 mg dexamethasone followed by ACTH test in 30 and 60 min were measured. Groups were stratified in relation to obesity, body fat distribution, and chronic complications. RESULTS: UFC and postdexamethasone cortisol were significantly increased in diabetic patients compared with both obese subjects (p < 0.01) and control group (p < 0.05), regardless to diabetic complications and obesity. Postdexamethasone cortisol was correlated with waist circumference. ACTH-induced cortisol levels were significantly higher in all type 2 diabetic patients. An independent association was found between AUC cortisol in ACTH test and insulin resistance. Multiple regression analysis showed that waist circumference was independently associated with sex, fasting plasma insulin, morning cortisol, and AUC of cortisol in ACTH test (R(2) = 0.334,p < 0.0000). CONCLUSIONS: In type 2 diabetic patients, the HPA axis is clearly hyperactive as evident in increased urinary free cortisol, diminished cortisol suppression after dexamethasone and increased ACTH-induced cortisol levels. Abdominal obesity and the presence of chronic complications increased the HPA axis hyperactivity in type 2 diabetes. Augmentation of positive feedback is associated with insulin resistance and negative feedback with abdominal obesity.

Insulin resistance and androgens in healthy women with different body fat distributions.

OBJECTIVE: To compare androgens and sex hormone-binding globulin (SHBG) levels, and indices of insulin sensitivity (the response of plasma insulin and C-peptide in OGTT, insulin resistance and beta-cell activity estimated with the homeostasis assessment model (HOMA model) in healthy obese premenopausal women with different body fat distributions. PATIENTS AND METHODS: Free testosterone, androstenedione, SHBG levels and responses of plasma glucose, insulin and C-peptide in OGTT were examined in 74 healthy premenopausal women (19 with lower-body obesity (WHR < 0.80), 20 with pure abdominal obesity (WHR > 0.85), 19 with predominant abdominal obesity (WHR 0.81-0.85) and 18 normal-weight women). Insulin resistance and beta-cell function were estimated with the HOMA model. RESULTS: Both fasting and glucose-induced insulin levels were higher in women with pure abdominal obesity than in the controls (p < 0.001) and in those with lower-body obesity (P < 0.01). Insulin resistance was also higher in women with pure abdominal obesity than in the controls (p < 0.01) and those with lower-body obesity (p < 0.05). Free testosterone (p < 0.01) was higher and SHBG (p < 0.001) was lower in women with abdominal obesity than in the control group and those with lower-body obesity. Insulin significantly correlated with SHBG, and this correlation was independent of androgens, obesity and obesity type. Beta-cell function positively correlated with free testosterone, whereas insulin resistance negatively correlated with SHBG, and was independent of obesity and obesity type. CONCLUSIONS: In healthy premenopausal women, increased BMI and more pronounced abdominal fat accumulation was associated with increased androgenic activity (higher free testosterone and lower SHBG levels) and with insulin resistance estimated using the HOMA model, as well as with increasing basal and glucose-induced insulin levels. SHBG levels correlated with insulin and insulin resistance independently of the degree of obesity, obesity type and androgens, whereas beta-cell function correlated only with free testosterone.