The phenomenon of HbA1c stability and the risk of hypoglycemia in long-standing type 1 diabetes.

AIMS: Hyperglycemia is the major factor underlying vascular complications of diabetes. Unfortunately, improved glycemia control is frequently accompanied by an increased risk of hypoglycemia. The aim of the study was to assess the relationship between hemoglobin A1c (HbA1c) and 1-week Continuous Glucose Monitoring (CGM) data in long-standing type 1 diabetes (T1DM). METHODS: We recruited 58 subjects with long-standing T1DM consecutively enrolled to the study. Each patient underwent a 1-week CGM and laboratory profile at baseline. Subjects were divided into three subgroups according to baseline HbA1c tertiles: T1 < 7.1%, T2 = 7.1-8.0%, and T3 > 8.0%. RESULTS: T1 patients were characterized by the longest time in range (66% of a week), whereas T3 patients experienced hyperglycemia in >50% time of the week. T1 patients were noted to have 25% of nighttime with glycemia <3.9 mmol/L (8% with glycemia <2.8 mmol/L). Most recent HbA1c closely reflected 10-years mean HbA1c values (R = 0.83; P < 0.0001). CONCLUSIONS: (1) Long-term diabetes control (10 years HbA1c mean) is a strong predictor of the current HbA1c levels. (2) Current and historical HbA1c levels are closely linked to CGM-derived glycemia. (3) Risk of clinically significant hypoglycemia negatively correlates with HbA1c. (4) HbA1c > 8.0% is associated with unsatisfactorily low (44%) time in range.

Subclinical Inflammation and Endothelial Dysfunction in Patients with Chronic Pancreatitis and Newly Diagnosed Pancreatic Cancer.

BACKGROUND: Recent studies have suggested that various cytokines may be important players in the development and progression of chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC). AIMS: We studied endothelial dysfunction and subclinical inflammation in patients with newly diagnosed pancreatic adenocarcinoma and CP. METHODS: A total of 45 patients were included in the present investigation, 27 with CP and 18 with PC. In addition, the study included 13 age- and body weight-matched healthy subjects served as controls. In all subjects, plasma adiponectin, TNF-alfa, interleukin 6 (IL-6), interleukin 1beta (IL-1ß), E-selectin, thrombomodulin, adhesion molecules ICAM and VCAM, and endothelin-1 were assessed. RESULTS: PC and CP patients as compared with controls had significantly greater plasma adiponectin (13,292 and 12,227 vs 5408 ng/ml; p < 0.0003), TNF-alfa (22.1 and 23.1 vs 13 pg/ml; p < 0.0002), and IL-6 (6.6 and 7.3 vs 3.3 pg/ml; p < 0.0001). Moreover, there was significantly higher concentration of ICAM (931 and 492 vs 290 ng/ml; p < 0.005) and VCAM (1511 and 1080 vs 840 ng/ml; p < 0.01) in PC and CP patients. When PC and CP patients with and without diabetes were considered separately, there was no difference in adiponectin, cytokines, and parameters of endothelial dysfunction. CONCLUSION: In summary, our data indicate that patients with CP and PC express high levels of several cytokines compared with healthy individuals, especially adiponectin, TNF-α and IL-6. Serum TNF-α and ICAM concentrations coordinately increase in advanced CP. Furthermore, especially in PC subjects, elevated markers of endothelial dysfunction are present. This study provides additional evidence that changes in inflammatory cytokine and adhesion molecules in PC and CP are not likely related to endocrine disorders.

Genetic and environmental predictors of chronic kidney disease in patients with type 2 diabetes and diabetic foot ulcer: a pilot study.

Chronic kidney disease (CKD) is often observed among patients with type 2 diabetes mellitus (T2DM) and diabetic foot (DF) leading to end stage renal disease. The aim of this pilot study was to determine genetic and environmental factors involved in the etiology of CKD among patients with DF. The following polymorphisms were studied: rs1800469, rs759853, rs1553005, rs1799983, rs1801133, rs3134069, rs2073618, rs8192678, rs6330, rs11466112, rs121917832 in terms of alleles distribution in patients with DF and T2DM, with or without CKD. The study includes 101 patients with T2DM and DF. Studied groups were divided into 39 individuals with CKD (cases) and 62 controls, depending on the presence of kidney failure defined as eGFR < 60ml/min/1.73m(2) and coexistence of microalbuminuria > 30 mg/dl in at least 3 urine samples. Cases and controls were matched according to mean age, gender, mean duration of T2DM, mean duration of insulin therapy, mean duration of DF cholesterol levels and smoking frequencies. The study showed that CKD risk factors were the following variables: creatinine level, body weight, hips circumference, ischemic heart disease, hypertension and diabetic retinopathy. Moreover, the results suggest the protective role of the allele C of rs3134069 polymorphism in CKD development in patients with T2DM and DF in the following allelic variants: [AA] vs. [AC] and [AA] vs. [AC + CC]. The allele C was observed to be less frequent than the allele A in patients with T2DM and DF. None of the other following polymorphisms was observed to be a potential risk factor of CKD in T2DM and DF population: rs6330, rs759853, rs1553005, rs1799983, rs1801133, rs1800469, rs8192678, rs11466112, rs121917832. We concluded that the rs3134069 polymorphism seems to be the most likely protective genetic factor in CKD development in patients with T2DM and DF.

Blood pressure disturbances and endothelial dysfunction markers in children and adolescents with type 1 diabetes.

OBJECTIVE: Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. METHODS: The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. RESULTS: Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). CONCLUSIONS: Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.

Prevalence of diabetes and impaired fasting glucose in Poland--the NATPOL 2011 Study.

AIMS: The aim of the analysis was to assess the prevalence of diabetes and impaired fasting glucose in Poland. METHODS: A questionnaire survey on a representative sample of 2411 Polish adults, complemented by blood pressure, anthropometric and fasting plasma glucose measurements. The research was part of the national cross-sectional NATPOL 2011 Study. Diabetes was assessed as self-reported (diagnosed) or screened (fasting plasma glucose level ≥ 7 mmol/l, based on one blood draw). RESULTS: Total prevalence of diabetes in 2011 was 6.7% (95% CI 5.6-7.9); 6.4% (95% CI 5.0-8.0) in women and 7.0% (95% CI 5.4-8.8) in men and did not change from 2002 (6.8%, 95% CI 95% CI 5.8-7.9). Over one quarter of individuals with diabetes were not aware of having the condition. Obesity, arterial hypertension and male gender were strong predictors of screened diabetes. Total prevalence of impaired fasting glucose in the surveyed population was 15.6% (95% CI 14.0-17.2). CONCLUSIONS: The prevalence of diabetes in Poland is similar to that observed in other European populations and has not changed over the last decade. The fact that every fourth person with diabetes is unaware of the disease creates important opportunities for screening and detection of the disease.

Plasma glucose after stomach or jejunum glucose infusion in Roux-en-Y gastric bypass patients--a possible implication for early satiety mechanism.

BACKGROUND: Morbidly obese patients undergoing gastric bypass surgery experience early satiety soon after the surgery; the mechanism of this effect is poorly understood. As blood glucose concentration plays a role in appetite regulation in humans, we hypothesized that after gastric bypass surgery glucose absorbed mainly in jejunum leads to a greater rise in plasma glucose that if it is ingested in stomach. MATERIAL AND METHODS: 24 non-diabetes morbidly obese patients (15 women, 9 men, mean age [± SD] 35.6 ± 11.9 years, body weight 140.7 ± 33.1 kg, BMI 46.8 ± 8.3 kg/m²) undergoing Roux-en-Y gastric bypass surgery were given 10 ml of 40% glucose solution to the stomach before its size reduction and to the jejunum after gastro-jejunal anastomosis was formed. RESULTS: After jejunal infusion blood glucose increased more rapidly and was ∼30% higher than after stomach infusion. Moreover, this increase was less pronounced in more obese patients. CONCLUSION: In patients after Roux-en-Y gastric bypass surgery glucose absorbed in jejunum leads to greater rise in plasma glucose concentration than if it is ingested in stomach. This phenomenon may help explain satiety feeling occurring early in gastric bypass surgery patients.

Age effect on vascular reactivity in Type 1 diabetes.

AIM: The objective of this study was to assess the effect of age on vascular reactivity in patients with Type 1 diabetes. METHODS: Forty-five patients with Type 1 diabetes and 71 healthy control subjects, divided into three age groups (18-30, 31-45 and 46-60 years old), underwent assessment of vascular reactivity based on ultrasound examination of a brachial artery after nitric oxide donor administration. RESULTS: The vasodilative and haemodynamic effect was most pronounced in the youngest control subjects, where lumen widening of 0.51 ± 0.16 mm (13.9 ± 4.2%) and increase in early velocity of 28.4 ± 6.5 cm/s (237 ± 55%) were observed, while, in the control subjects from the middle and oldest age groups, the increase in artery diameter was 0.4 ± 0.11 and 0.22 ± 0.12 mm (9.8 ± 2.6 and 5.0 ± 2.6%), respectively. In the youngest patients with diabetes, lumen widening by 0.35 ± 0.13 mm (8.6 ± 3.4%) and increase in early diastolic velocity by 16.9 ± 5.6 cm/s (158 ± 52%) were noted (P < 0.05 vs. control subjects). In patients with diabetes from the middle and oldest age groups, the increase in artery diameter was 0.26 ± 0.06 and 0.16 ± 0.09 mm (5.5 ± 1.4 and 3.2 ± 1.8%), respectively. CONCLUSIONS: Vascular reactivity is strongly age dependent in all subjects; however, responses are delayed and occur over a longer time period in the patients with diabetes. Vasodilation test protocols should take into account the age of the subjects.

Decreasing concentration of interstitial glucose in REM sleep in subjects with normal glucose tolerance.

AIMS: Sleep is divided into two major stages, non-rapid eye movement (NREM) and rapid eye movement (REM), which are distinct in various neuroendocrine respects. NREM/REM cycles influence insulin and glucagon secretion; however, glucose concentrations in REM compared with NREM have not been directly explored. The aim was to investigate the differences in glucose concentrations in interstitial fluid (IGC) between NREM/REM cycles using a continuous glucose monitoring system (CGMS). METHODS: Thirteen subjects were eligible for analysis out of the 28 enrolled. All underwent standard polysomnography for the assessment of sleep stages and the exclusion of sleep apnoea syndrome with CGMS and subsequent morning oral glucose tolerance test (exclusion of glucose intolerance or diabetes). RESULTS: The IGC in REM fell in 12 out of the 13 subjects, whereas the IGC in NREM increased in eight out of the 13 subjects. Therefore, the mean change of IGC differed in direction between sleep stages: -0.028 (-0.045 to -0.011) for REM vs. 0.005 (-0.012 to 0.017) for NREM [median (QR), P = 0.007, n = 13], with the mean difference of 0.038 mmol/l x 5 min(-1) (95% confidence interval 0.012, 0.064). The mean glucose concentration in REM sleep was lower than in NREM: 4.29 +/- 1.00 vs. 4.53 +/- 0.90 mmol/l (mean +/- sd, P = 0.003, n = 13). CONCLUSIONS: The decrease in IGC in REM compared with NREM sleep, with lower absolute values, may arise from different physiological events observed in these sleep stages. The REM-related decline in glucose concentrations may be a risk factor for nighttime hypoglycaemia.

Distribution of the components of the NCEP ATP III-defined metabolic syndrome in newly diagnosed diabetes and non-diabetes caucasian subjects; implications for metabolic syndrome prevention and treatment.

UNLABELLED: The study aimed at assessing the relationship between five components of the NCEP ATP III-defined metabolic syndrome (MS) in diabetes and non-diabetes MS subjects. METHODS: Prevalence of MS and its components was assessed in 1586 adult Caucasian individuals, without known diabetes. Oral glucose tolerance test (OGTT) with 75 g glucose according to WHO protocol was conducted in all subjects. RESULTS: MS was diagnosed in 419 persons (prevalence 26.4%), including 123 subjects with newly diagnosed diabetes. Diabetes subjects presented with higher plasma triglycerides and slightly more pronounced abdominal obesity as well as higher fasting plasma insulin, which in all reflected insulin resistance-related character of MS pathophysiology. However, the distribution of MS components was largely uneven in diabetes and non-diabetes subjects. Elevated plasma triglycerides and low HDL cholesterol were the most prevalent components. The least often found component was elevated fasting plasma glucose (FPG). Non-diabetes subjects with elevated FPG were more likely to present with three or four other components than with two of them only. In contrast, those with high plasma triglycerides, low plasma HDL cholesterol or increased waist circumference were all more likely to have two rather than three or four other MS components. Subjects with diabetes presented significantly more often with four or five MS components when compared with non-diabetes subjects. CONCLUSIONS: The components of metabolic syndrome are not equally prevalent in Caucasian population. Lipid disorders are most often found and glucose intolerance is the least prevalent MS component. Glucose intolerance and diabetes occurred in a more complex setting, concomitantly with three or four other MS components, suggesting that diabetes is associated with more advanced stages of MS. These findings may have important implications for MS prevention and treatment.

Loss of taste-induced hypertension--caveat for taste modulation as a therapeutic option in obesity.

OBJECTIVE: Effective treatment of obesity is extremely difficult, and taste modulation has been suggested as a feasible option. We aim at presenting dangers associated with stroke-induced taste impairment. METHODS: A case report is presented with clinical and laboratory findings. We review literature on the effect of taste modulation on body weight. RESULTS: Eight months after suffering stroke, a 63-year old obese woman with a nine year-old history of type 2 diabetes reported headache and poor general feeling. Physical examination revealed significantly elevated blood pressure of 190/110 mmHg. The patient had never had elevated blood pressure before nor ever been taking any antihypertensive medication. However, stroke resulted in severe persisting dysgeusia. We found out that she had been using up to 110 g of salt daily to make her meals palatable. Standard gustatory tests confirmed severe taste impairment, reflecting the lesion of the glossopharyngeal nerve. Taste loss was not associated with body weight reduction. Limiting daily salt intake to 5 g within 4 weeks resulted in lowering blood pressure to 120/70 mmHg. CONCLUSION: Stroke-induced dysgeusia may lead to increased salt intake in a type 2 diabetes patient, which caused development of severe hypertension. The taste loss did not yield any weight reduction. We suggest that aiming at reducing body weight by means of taste modulation should be done with caution. Physicians must be aware that patients may try to overcome dysgeusia by additional salt intake, if not adequately informed of the risk thereof.

Randomized clinical trial of postoperative hernia prophylaxis in open bariatric surgery.

BACKGROUND: Postoperative hernia following bariatric procedures is more common than in other groups of surgical patients, and remains a serious problem. Gastric bypass is the most often performed bariatric procedure and, despite the increasing popularity of a laparoscopic approach, many morbidly obese patients are still offered open procedures. The aim of this study was to assess the effects of prophylactic polypropylene mesh in morbidly obese patients undergoing gastric by-pass surgery. METHODS: The study randomized 74 patients undergoing open Roux-en-Y gastric bypass into two groups: wound closure with (n = 36) or without (n = 38) a polypropylene mesh. Mean(s.d.) body mass and body mass index in the mesh group were 137.3(24.5) kg and 46.2(7.1) kg/m(2) and in the non-mesh group were 139.0(24.9) kg and 46.8(7.6) kg/m(2) respectively. In the non-mesh group, the wound was closed with a polypropylene suture. Patients in the mesh group had in addition a polypropylene mesh inserted in a sublay manner. RESULTS: Patients were followed up for at least 6 (range 6-38) months. Hernia developed in eight patients in the non-mesh group but in none in the mesh group. The duration of hospital stay was similar in both groups: mean(s.d.) 8.4(3.2) and 10.3(5.9) days (P = 0.092). There were no serious complications in either group. CONCLUSION: The use of a mesh prevented hernia development and did not lengthen hospital stay.

Diagnostic difficulties in long-standing insulinoma with near-normal plasma insulin levels.

Insulinoma tumors are often difficult to detect, as the symptoms largely precede occurrence of a visualized tumor. We report the case of an insulinoma patient with long delayed diagnosis and marked adaptation to extreme hypoglycemia. The patient with a 7-yr history of seizures was found to have plasma glucose concentration during a starvation test as low as 16 mg/dl, with no clinically significant symptoms and concomitant normal plasma insulin levels: 10-30 microIU/ml. All attempts to localize a tumor with repeated abdominal ultrasound examinations or computed tomography scanning were unsuccessful. The patient did not tolerate the introduced oral treatment with diazoxide. Once it had become technically available, endoscopic ultrasonography of the pancreas was performed. It revealed a 10 mm tumor in the pancreatic head. The tumor was subsequently removed surgically. During the operation plasma insulin concentration rose almost 15-fold, which confirmed the insulin-secreting character of the growth. Microscopic examination revealed benign insulinoma, with partially trabecular structure. One month after the operation the patient had normal plasma glucose values of 60-120 mg/dl, but she constantly complained of excessive thirst, which occurred soon after the operation and slowly subsided in the following weeks. In conclusion, the present report demonstrates that insulinoma should be considered and searched for in every case of hypoglycemia associated with normal insulin levels. It also confirms the essential role of endoscopic ultrasonography in the diagnosis of insulin-secreting tumors.

Diabetes screening after gestational diabetes mellitus: poor performance of fasting plasma glucose.

Gestational diabetes mellitus (GDM) is an established risk factor for the development of overt diabetes. Since the change in diagnostic criteria for diabetes in 1997, it is unclear whether there should be any preference for fasting or post-glucose challenge blood glucose in diagnosing diabetes after GDM. The study aimed at assessing the usefulness of both diagnostic methods in women after GDM. The study enrolled 193 women with previous GDM. Women who did not have a current diagnosis of diabetes were screened for impaired fasting glucose (IFG) and for glucose intolerance with an oral 75-g glucose tolerance test. A total of 45 (23.3%) subjects declared to be already diabetic. Of the 148 non-diabetic subjects, 141 (95.3%) had normal fasting plasma glucose, whereas four (2.8%) had IFG (i.e. FPG> or =6.1 and <7.0 mmol/l) and 3 (2.5%) had FPG> or =7.0 mmol/l. Upon OGTT, among the 141 subjects with normal FPG, 6 (4.3%) were diagnosed with diabetes and 23 (16.3%) with impaired glucose tolerance (IGT); the remaining 112 (79.5%) had normal glucose tolerance. Three out of four subjects with IFG had IGT. The sensitivities of fasting criteria for diagnosis of diabetes and IFG/IGT were 14.3% (95% CI, 8.0%-37.2%) and 17.1% (95% CI, 8.6%-19.8%), respectively. The specificities were 98.6% (95% CI, 97.9%-99.7%) and 99.1% (95% CI, 96.5%-100%), respectively. The kappa for diabetes diagnosis was 0.177 (95% CI, 0.018-0.507). For women with previous GDM, the sensitivity of the new criteria based upon fasting plasma glucose is unacceptably low. In addition, the two sets of criteria are not interchangeable. Therefore, we suggest full glucose tolerance diagnostic procedures in women after GDM, including assessment of post-glucose challenge values.

Plasma total homocysteine concentrations in adults with growth hormone (GH) deficiency: effects of GH replacement.

Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an independent cardiovascular risk factor, thus potentially contributing to benefits of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8 male), mean age 39-years, with GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. After an overnight fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4), creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2) and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical statistical models, univariate and multivariate correlation. GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068, p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/-0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once individuals had achieved 'adequate' GH replacement, was no longer significantly different (p=0.090). When separated by gender, at 6 months (V3) there was a small, but significant increase in Hcy in men (p=0.028), but not in women (p=0.58). There was no significant change in B12, folate, free T4 or creatinine levels. Univariate analysis revealed that only B12 and folate showed significant negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate: parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple variable model, both B12 and folate remained significantly negatively associated with plasma total homocysteine (p=0.018; p<0.001, respectively). In this observational study normalisation of IGF-1 levels in adult subjects with growth hormone deficiency was not associated with a fall in total homocysteine. Before firm conclusions can be drawn about the contribution of changes in plasma homocysteine concentrations to cardiovascular prognosis in adult GHD patients receiving GH replacement, further controlled studies are required.