Modern Management of Cardiometabolic Continuum: From Overweight/Obesity to Prediabetes/Type 2 Diabetes Mellitus. Recommendations from the Eastern and Southern Europe Diabetes and Obesity Expert Group.

The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in ß-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.

Intermittent Use of Continuous Glucose Monitoring: A New Paradigm in Treatment of Type 2 Diabetes.

OBJECTIVES: To suggest how continuous glucose monitoring (CGM) may be used intermittently in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: The use of CGM is largely in those with type 1 diabetes (T1D), in whom it makes sense to use CGM continuously as CGM provides a valuable tool to not only adjust their insulin doses but also to match it with their diet, physical activity, and other lifestyle modifications. In the case of T2D, however, especially for those not on insulin, the use of CGM may not be needed on a continuous basis. The use of CGM on an intermittent basis is rarely discussed in the literature. This article tries to provide clinical situations where CGM can be used intermittently. RESULTS: Intermittent use of CGM defined as the "use of CGM once in 2 or 3 months or a fixed frequency," and may be useful in several situations in those with T2D. We suggest the following indications for the intermittent use of CGM in T2D-newly diagnosed patients where treatment is being started, uncontrolled diabetes where treatment is being altered, starting intensive lifestyle modification, during infections, during preoperative control, in children and adolescents with T2D, as a motivational tool to improve behavioral modification, after metabolic surgery, and in patients on steroids, apart from other indications. CONCLUSION: Intermittent use of CGM in T2D can be useful in special situations and can also be cost saving particularly in resource-constrained regions of the world.

Management of obesity in the times of climate change and COVID-19: an interdisciplinary expert consensus report.

Obesity is a chronic disease associated with increased metabolic and cardiovascular risk, excessive morbidity and mortality worldwide. The authors of the present consensus, clinicians representing medical specialties related to the treatment of obesity and its complications, reviewed a number of European and American guidelines, published mostly in 2019-2021, and summarized the principles of obesity management to provide a practical guidance considering the impact that increased adiposity poses to health. From a clinical perspective, the primary goal of obesity treatment is to prevent or slow down the progression of diseases associated with obesity, reduce metabolic and cardiovascular risk, and improve the quality of life by achieving adequate and stable weight reduction. However, obesity should be not only considered a disease requiring treatment in an individual patient, but also a civilization disease requiring preventive measures at the populational level. Despite the evident benefits, obesity management within the health care system-whether through pharmacotherapy or bariatric surgery-is only a symptomatic treatment, with all its limitations, and will not ultimately solve the problem of obesity. The important message is that available treatment options fail to correct the true drivers of the obesity pandemic. To this end, new solutions and efforts to prevent obesity in the populations are needed.

Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes.

PURPOSE: Optimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats with streptozotocin-induced diabetes. METHODS: The study was conducted on 200 male Wistar rats with streptozotocin-induced diabetes. In the last phase of the study, 45 rats, with the most stable glucose levels in the range of 350-500 mg/dL, were divided into three groups: group I received human non-protamine insulin subcutaneously (5 IU/kg body mass) once a day, group II received metformin intragastrically (500 mg/kg b.m.), and group III (control) was given saline subcutaneously. After 14 days of antidiabetic treatment, a 2 cm × 2 cm thin layer of skin was cut from each rat's dorsum and a 4 cm disk with a hole in its center was sewn in to stabilize the skin and standardize the healing process. The wound healing process was followed up for 9 days, with assessment every 3 days. Biopsy samples were subjected to hematoxylin and eosin staining and immunohistochemical assays. RESULTS: Analysis of variance revealed significant influence of treatment type (insulin, control, or metformin) on the relative change in wound surface area. The wound healing process in rats treated with insulin was more effective than in the metformin and control groups. Wound tissue samples taken from the insulin-treated animals presented significantly lower levels of inflammatory infiltration. Immunohistochemical assessment showed the greatest density of centers of proliferation Ki-67 in insulin-treated animals. CONCLUSION: These results suggest that an insulin-based treatment is more beneficial than metformin, in terms of accelerating the wound healing process in an animal model of streptozocin-induced diabetes.

The MDR1/ABCB1 gene rs 1045642 polymorphism in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most frequently diagnosed tumors in Western countries. CRC is a heterogeneous group of tumors with regards to its molecular pathogenesis and genetic factors. Both genetic variations and anthropometric factors may affect morbidity in CRC patients. The aim of this study was to assess the impact of multidrug resistance 1/ATP-binding cassette sub-family B member 1 gene (MDR1/ABCB1) polymorphism rs1045642 and general anthropometric factors on the CRC risk. MATERIAL AND METHODS: The study included 250 patients who underwent colonoscopy and polypectomy between 2006 and 2013 in a single endoscopy unit in Warsaw, Poland. RESULTS: The CRC was diagnosed in 50 individuals, and 200 patients were included in the control group. Cases and controls were matched for mean age and sex (p > 0.05). Factors that were found to significantly increase the risk of CRC were ulcerative colitis (8/35 in the CRC group vs. 8/181 in the control group; p = 0.001), family history of CRC (11/33 vs. 26/172; p = 0.05), and diabetes mellitus (12/34 vs. 28/170; p = 0.04). Allele T of the rs 1045642 polymorphism was more frequently present in CRC cases (in both a co-dominant and recessive model) and in males (in a co-dominant model), although these associations were not statistically significant (p > 0.05). CONCLUSIONS: The MDR1/ABCB1 gene polymorphism rs 1045642 may be involved in the pathogenesis of CRC and this relationship may be sex-specific for males. However, further population studies are necessary to assess this relationship.

Roux-en-Y gastric bypass as a cure of iatrogenic - steroid induced diabetes.

BACKGROUND: Steroid-induced diabetes (SIDM) is a frequently found clinical condition since steroid-based therapies continue to be widely used in hospital and ambulatory care. Recommended optimal treatment of SIDM includes similar glucose lowering strategies as in type 2 diabetes. This typical management cannot cure the disease, it can only control blood glucose. Recently, bariatric surgery has emerged as an effective treatment for type 2 diabetes mellitus. However, up to now, the usefulness of bariatric surgery in treatment of SIDM has not been evaluated. CASE REPORT: A 49-year-old female oncologic patient with steroid induced diabetes was referred for surgical treatment to the Department of General and Transplant Surgery in November 2009. Six years earlier, she underwent successful oncologic treatment with cladribine and high doses of steroids due to hairy cell leukemia. Finally complete hematologic remission with normalization of morphology and reduction of spleen size has been obtained. Prior to steroid treatment, blood glucose and urine examinations were within normal range. The patient was non-obese and had no family history of diabetes. Nevertheless, the patient developed diabetes secondary to corticosteroid therapy, poorly controlled by oral hypoglycemic agent (acarbosum), successfully converted to insulin therapy. Upon admission to the Department of General and Transplant Surgery, the patient was treated with 58 units of insulin per day. The patient was scheduled for Roux-en-Y gastric bypass (RYGB). Insulin was withdrawn immediately after the surgery and within six months after the surgery, plasma glucose and glycated hemoglobin (HbA1c-5.5%) levels reached and remained within normal range. Currently, eight years after surgery, body weight and BMI are 80 kg and 27.68 kg/m2, respectively. Plasma glucose and glycated hemoglobin are also normal. Importantly, from an oncological point of view, the patient has remained in continuous complete remission since October 2003. CONCLUSIONS: Our report is the first to our knowledge describing the effect of gastric bypass surgery on SIDM in a patient with prior hematologic malignancy. It proves that surgically altered anatomy of the small intestine improves glucose homeostasis previously disturbed with pro-diabetic medication.

Differences in risk factors of malignancy between men and women with type 2 diabetes: A retrospective case-control study.

BACKGROUND: The aim of this multicenter, retrospective, case-control study was to identify differences in risk factors of malignancy between men and women with type 2 diabetes. RESULTS: Among women the most prevalent malignancies were: breast and uterine cancers (35.6% and 14.4% respectively), while among men there were: colorectal and prostate cancers (24.5% and 13.3% respectively). In both gender metformin use was associated with lower cancer risk. Obesity and insulin treatment in dose-dependent and time-varying manner were associated with significantly increased risk of malignancy in females. In men, unexpectedly, cardiovascular disease was more prevalent in control group. Other variables did not show significant association with malignancy risk. MATERIALS AND METHODS: 118 women and 98 men with type 2 diabetes mellitus who developed cancer after diagnosis of diabetes and the same number of strictly age matched controls with type 2 diabetes and without malignancy were included into the study. Diabetes duration, antidiabetic medications use, glycated hemoglobin level, body mass index, smoking habits, occupation, presence of comorbidities and aspirin use were included into analyses. CONCLUSIONS: Metformin demonstrated protective effect against cancer in both sexes. Obesity and insulin treatment seem to have greater impact on cancer risk among women.

Role of the rs2274907 allelic variant of the ITLN1 gene in patients with diabetic foot.

INTRODUCTION Diabetic foot (DF) is a serious complication of diabetes mellitus (DM) that occurs due to neuropathy or atherosclerosis of the lower limbs. Omentin (encoded by the ITLN1 gene) has been implicated as a protective factor in vascular complications of diabetes, likely due to its endothelial vasodilator activity and its anti­inflammatory actions. However, susceptibility to DF with respect to the allelic variants of the ITLN1 gene has not been studied so far. OBJECTIVES This study aimed to evaluate the association between the rs2274907 allelic variant of the ITLN1 gene and the occurrence of DF in patients with type 2 diabetes mellitus (T2DM).  PATIENTS AND METHODS The study included 670 individuals: 204 with T2DM and DF (DF group), 299 with T2DM without DF (T2DM group), and 167 healthy controls.  RESULTS Ischemic heart disease, retinopathy, nephropathy, neuropathy, obesity, hyperlipidemia, and active smoking were more frequent in the DF group than in the T2DM group. Allele A of the rs2274907 variant was observed more frequently in the DF group compared with healthy controls in an additive model (odds ratio [OR] = 0.7, P = 0.034). This effect was also sex­specific for males in both the additive and recessive models (OR = 0.6, P = 0.015 and OR = 0.52, P = 0.0017, respectively). However, no differences in the distribution of alleles was observed between the DF and T2DM groups. CONCLUSIONS The rs2274907 variant of the ITLN1 gene is associated with increased prevalence of DF.

Risk factors for cancer development in type 2 diabetes: A retrospective case-control study.

BACKGROUND: The risk of several types of cancer is increased in type 2 diabetes mellitus. The earliest possible diagnosis of cancer - difficult within regular outpatient diabetes care - is of utmost importance for patients' survival. The aim of this multicenter, retrospective (years 1998-2015), case-control study was to identify risk factors associated with malignancy in subjects with diabetes treated in a typical outpatient setting. METHODS: In the databases of 3 diabetic and 1 primary care clinics 203 patients (115 women) with type 2 diabetes mellitus who developed malignancy while treated for diabetes were identified. The control group consisted of 203 strictly age- and gender matched subjects with type 2 diabetes without cancer. Factors associated with diabetes: disease duration, antidiabetic medications use and metabolic control of diabetes were analyzed. Also other variables: BMI (body mass index), smoking habits, place of residence and comorbidities were included into analysis. RESULTS: The most prevalent malignancies in men and women together were breast cancer (20.7 %) and colorectal cancer (16.3 %). HbA1c (hemoglobin A1c) level ≥8.5 %, obesity and insulin treatment in dose-dependent and time-varying manner demonstrated significant association with increased risk of malignancy, while metformin use was associated with a lower risk of cancer. Diabetes duration, comorbidities, smoking habits, place of residence and aspirin use did not show significant association with risk of malignancy. CONCLUSIONS: In the outpatient setting the obese patients with poorly controlled insulin treated type 2 diabetes mellitus should be rigorously assessed towards malignancies, particularly breast cancer in women and colorectal cancer in men.

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma.

AIM: To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers. METHODS: The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-ß1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification. RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-ß1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-ß1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-ß1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043). CONCLUSION: Serum TGF-ß1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-ß1 may be useful to predict endocrine insufficiency in PDAC.

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

INTRODUCTION: Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. AIMS: We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. METHODS: The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). RESULTS: Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found. CONCLUSION: The results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders.

Personal history of obesity matters. Adolescent adiposity may influence the late results of gastric bypass performed in adults.

INTRODUCTION: The influence of adolescent obesity on weight loss following bariatric surgery in adults has not been evaluated. The purpose of this study was to determine the impact of prior adolescent obesity on long-term weight changes following Roux-en-Y gastric bypass (RYGB) in adulthood. MATERIAL AND METHODS: This single centre retrospective cohort study evaluated changes in body mass index (BMI) after RYGB within 9-13 years. Questionnaires were sent by post to patients (n = 147) operated on between January 1999 and December 2003 in the Department of General and Transplant Surgery of Medical University, Lodz, Poland. Long-term data was obtained from 33.33% (n = 49, mean age 46.1 ± 10.7 years). Preoperative, nadir and actual BMI and differences between these values were calculated. Data was analysed with a cut-off BMI at 18 years old of 30 and 35 units (U). RESULTS: Patients with a BMI of more than 30 and 35 U in adulthood regained more weight after initial achievement of nadir total weight loss compared to their only adult obese counterparts. Preoperative BMI varied by weight at 18 years old (p = 0.02), while value and time to nadir postoperative BMI and actual BMI were comparable. CONCLUSION: Adolescent obesity may be a risk factor for long-term RYGB failure. Surgery cannot be definitively curative in this group of patients, and continued active conservative treatment is required.

The impact of the repair of staple line dehiscence in post-RYGB patients on glucose homeostasis and gut hormones--a preliminary study.

INTRODUCTION: Staple-line disruption (SLD) following Roux-en-Y gastric bypass (RYGB) results in weight regain. This study evaluated glucose homeostasis and gut hormonal changes following surgical repair of gastrogastric fistula. MATERIAL AND METHODS: Three patients with SLD underwent an oral 75 g glucose tolerance test (OGTT) before (baseline) and one week after gastric pouch restoration. Plasma glucose, insulin and glucagon glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1) were measured in the OGTT samples. Fasting plasma levels of ghrelin and leptin were assessed. RESULTS: Restoration of gastric pouch provided moderate amelioration of glucose metabolism and gut hormones, yet without complete normalisation of glucose homeostasis at one week after surgery. Duodenal passage exclusion resulted in early improvement of control fasting plasma glucose with decrease of glucagon from 18.5 to 15 (ng/mL, by 19%), relatively stable insulin and decline of incretin hormones (GIP and GLP-1). Post-challenge measurements confirmed amelioration of glycaemic control with decrease of plasma glucose from 182 to 158 mg/dL at 60 minutes. Surgical re-intervention resulted in exacerbation of GIP response with brisk rise in plasma level, accompanied by considerable increase of peak insulin concentration. The overall post-challenge glucagon and GLP-1 responses were decreased. Marked decrease in fasting plasma ghrelin and leptin were observed. CONCLUSIONS: Our report gives further insight into the hormonal mechanisms underlying the effects of surgically altered anatomy of different parts of the small intestine on glucose homeostasis that is highly important, since it may facilitate novel conservative therapies of diabetes without the need for surgery.

Major liver resection results in early exacerbation of insulin resistance, and may be a risk factor of developing overt diabetes in the future.

PURPOSE: This single center prospective cohort study evaluated the influence of hemihepatectomy on glucose homeostasis. METHODS: The study included 30 patients undergoing hemihepatectomy. All patients underwent an oral 75 g glucose tolerance test before (baseline), 1 week and 1 month after the surgery. Plasma glucose, insulin and glucagon were measured in the OGTT samples, and the HOMA index was calculated. The fasting levels of interleukin 6 and 1ß, tumor necrosis factor and adiponectin were assessed. RESULTS: The fasting plasma and 120-min post-challenge mean glucose level increased during the study from 89.6 to 103.5 mg/dl (by 15.5 %) and from 136.4 to 162.2 (by 18.9 %; p = 0.51), respectively, accompanied by an increase in fasting glucagon (from 3.2 to 5.9 ng/mL; p = 0.043) and insulin (from 14.6 to 19.3 IU/mL) and by a decrease in plasma insulin at 60 min of OGTT (p = 0.34). An increase of IL-6 (p = 0.015) and TNF (from 49.7 to 53 pg/mL), and decrease of plasma APO (7658 to 5152 ng/mL) and exacerbation of insulin resistance (p = 0.007) were noted. CONCLUSION: Hemihepatectomy resulted in moderate disturbances in glucose homeostasis, in a majority of patients that was likely to be of minor clinical relevance. However, the patients might be at higher risk of developing overt diabetes following long-term survival.

Rosiglitazone treatment in nondiabetic subjects with nonalcoholic fatty liver disease.

INTRODUCTION: Pharmacological treatment options for nonalcoholic fatty liver disease (NAFLD) are limited. It has been suggested that thiazolidinediones may be useful in NAFLD treatment. OBJECTIVES: An open-label prospective study was conducted to assess the efficacy and safety of rosiglitazone treatment in nondiabetic subjects with NAFLD. PATIENTS AND METHODS: A total of 27 subjects (mean age 44 ± 11 years, body mass index 29.2 ± 3.1 kg/m2), with biopsy-confirmed NAFLD and no other complaints, were treated with rosiglitazone 4 mg daily for 6 months. RESULTS: No adverse events were observed during a 6-month treatment with rosiglitazone. Liver enzymes gradually decreased (alanine transaminase from 101 ± 59 to 58 ± 39 IU/l, aspartate transaminase from 52 ± 24 to 37 ± 15 IU/l; P <0.001). Plasma insulin levels decreased significantly by 30% to 50% in each time point of the oral glucose tolerance test. The homeostatic model assessment index decreased from 3.73 ± 1.89 to 2.06 ± 1.68 (P <0.001). No significant changes in plasma glucose were noted. Plasma adiponectin increased from 2198 ± 1853 to 5734 ± 1999 ng/ml (P <0.001). There were no statistically significant changes in body weight, glycated hemoglobin A1c, plasma lipids, or leptin. CONCLUSIONS: Rosiglitazone treatment in patients with NAFLD is safe, well-tolerated and leads to a significant improvement in liver function and insulin sensitivity, without adversely affecting the lipid profile.

The prevalence of cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type 1 (SPINK1) gene mutations in Polish patients with alcoholic and idiopathic chronic pancreatitis.

BACKGROUND: The main cause of chronic pancreatitis (CP) is excessive alcohol consumption. On the other hand, only 5-10% of heavy drinkers develop chronic pancreatitis. We have only limited information regarding the pathogenic mechanism by which alcohol leads to the disease. Mutations of the PRSS1 and SPINK 1 have been mostly implicated in hereditary and idiopathic CP, but their presence in other types of this disease have also been reported. AIMS: The aim of the study was to determine the frequency of PRSS1 and SPINK1 mutations in patients with chronic alcoholic (ACP) and idiopathic pancreatitis (ICP) as well as to investigate their relation to the clinical course of the disease. METHODS: The study included 33 ACP and 14 ICP patients as well 46 healthy subjects. The diagnosis of CP was based on clinical data, ultrasound, and computed tomography. After isolation of DNA from peripheral blood two trypsinogen mutations were detected N29I and R122H by allelo-specific amplification polymerase chain reaction (ASA-PCR) and by the PCR-restriction fragment length polymorphism (RFLP). Beside this N34S mutation of SPINK1 was analyzed by PCR restriction fragment length polymorphism (PCR-RFLP). RESULTS: PRSS1 mutations have been detected in 11 (33%) patients with ACP. The frequency of the PRSS1 mutations was higher in patients with ACP than in controls (4.3%) (p < 0.001). The frequency of PRSS1 mutation was present in 21.4% of ICP patients, which was significantly higher (p < 0.05) than in controls. Overall, six (18%) SPINK1 mutations in ACP group have been detected. Among 14 patients with ICP, in four (28.6%) of them SPINK1 has been detected. The same mutations have also been found in three (6.5%) control subjects. The frequency of the N34S mutation was higher in patients with ICP than in the controls (p < 0.05), but the frequency of N34S mutation did not differ between ACP and the control group. No relations have been detected between PRSS1 and SPINK1 mutations presence and clinical course and complications of CP. CONCLUSIONS: Those preliminary data suggest the high prevalence of SPINK1 and PRSS1 mutations in the Polish population, generally, as well as in CP patients. It may be speculated that those mutations contribute to the development of chronic pancreatitis, especially in patients with alcohol overindulgence.

Long-term results of gastric bypass surgery in morbidly obese type 1 diabetes patients.

BACKGROUND: Long-term effects of bariatric surgery in morbidly obese type 1 patients are unknown. Five to eight-year experience in the case series of type 1 diabetes subjects is presented. METHODS: Three poorly controlled type 1 diabetes patients, aged 19, 23, and 28 underwent Roux-en-Y gastric bypass surgery. RESULTS: Their maximum body weight reduction noted during the follow-up was between 27% and 31% of baseline body weight, insulin requirement decreased from 0.6-0.95 to 0.3-0.83 IU/kg, and absolute reduction in HbA(1c) was 3-4%. Significant improvement in blood pressure, plasma lipid profile, and microalbuminuria was noted. CONCLUSIONS: RYGB surgery in morbidly obese type 1 diabetes patients leads to a significant and maintained weight loss and results in remarkable improvement in blood glucose control and concomitant disorders. Bariatric surgery should be recommended to significantly obese type 1 diabetes patients as a means of reduction of vascular complications risk.

Circadian blood pressure variation in normotensive type 2 diabetes patients and angiotensin converting enzyme polymorphism.

BACKGROUND/AIMS: Loss of circadian blood pressure (BP) variation (i.e., lack of nocturnal BP dip by at least 10mmHg, 'non-dipping') is associated with increased mortality rate in subjects with diabetes. We studied whether angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism may play a role in 24-h BP rhythm control. METHODS: The study group was 38 normotensive normoalbuminuric type 2 diabetes patients with impaired BP variation, the controls were 51 well-matched type 2 diabetes subjects with normal 24-h BP rhythm. ACE I/D polymorphism, endothelial function and subclinical inflammation parameters (serum endothelin-1, sE-selectin, intercellular and vascular cell adhesion molecules, tumor necrosis factor-alpha) were assessed. RESULTS: ACE DD genotype was found in 20 (53%), ID genotype in 16 (42%), and II genotype in 2 (5%) study group subjects, while 5 (10%) control subjects had DD genotype, 30 (59%) - ID genotype, and 16 (31%) - II genotype (p<0.0001). Study group subjects presented with marked endothelial dysfunction. CONCLUSION: Impaired circadian blood pressure variation in normotensive normoalbuminuric type 2 diabetes patients is associated with ACE DD genotype and marked endothelial dysfunction when compared to diabetic subjects with normal blood pressure rhythm.

Predicting maximum Roux-en-Y gastric bypass-induced weight reduction--preoperative plasma leptin or body weight?

BACKGROUND: Weight loss after bariatric surgery varies between patients, and predicting the extent thereof is often inaccurate. The aim of this study was to assess the potential of preoperative plasma leptin and body weight in predicting the maximum weight loss within 2 years after Roux-en-Y gastric bypass (RYGBP). METHODS: The study comprised 68 subjects (39 women, 29 men; mean age 36.4 +/- 10.2 years, body weight 130.3 +/- 24.8 kg, BMI 44.4 +/-6.8 kg/m2) undergoing RYGBP who were followed for 2 years. Baseline and maximum follow-up plasma leptin and weight were assessed. RESULTS: Mean maximum weight reduction of 50.5 +/- 19.1 kg (38.0 +/- 9.0%, range 24-100 kg) was noted at 15 +/- 4 months after RYGBP. Baseline plasma leptin was 37.9 +/- 14.5 ng/ml, and decreased to 17.4 +/- 8.1 ng/ml (P < 0.001) at maximum weight reduction. No significant correlation between baseline plasma leptin and absolute or relative weight reduction or minimum body weight achieved was noted. No significant plasma leptin threshold which would be predictive for any consistent extent of weight loss was found. However, baseline body weight was a strong determinant of minimum body weight attained (r = 0.67; P < 0.01) and of maximum absolute weight reduction (r = 0.81; P < 0.01). CONCLUSION: Preoperative plasma leptin concentration cannot be used as a predictor of weight reduction following RYGBP. Preoperative body weight is a reliable predictor of post-RYGBP weight loss.

Circadian blood pressure variation in morbidly obese hypertensive patients undergoing gastric bypass surgery.

BACKGROUND: Impaired blood pressure (BP) variation, often found in obesity and hypertension, is associated with increased cardiovascular risk. The effect of obesity surgery on BP variation is unknown. We performed this study to investigate the effect of gastric bypass surgery on circadian BP variation in morbidly obese hypertensive subjects. METHODS: The study group consisted of eight patients (mean age 35.0 +/- 9.1 years), with impaired circadian BP rhythm. Controls were eight well-matched subjects (34.6 +/- 9.8 years) with normal BP rhythm. All patients underwent gastric bypass surgery. The 24-h ambulatory BP measurements were performed before (baseline) and 8 weeks after gastric bypass surgery. RESULTS: Mean body weight in the study group and controls decreased from baseline of 129.0 +/- 21.9 kg and 134.1 +/- 27.2 kg to 116.7 +/- 21.1 kg (by 9.5% +/- 2.1%) and 121.6 +/- 25.7 kg (by 9.3% +/- 1.7%) after the surgery, respectively (P < .0001 v baseline). Mean 24-h, daytime, and night-time BP values decreased significantly and similarly in both groups. In the study group mean 24-h systolic and diastolic BP decreased from 154.7 +/- 12.3 mm Hg and 105.6 +/- 8.1 mm Hg to 138.5 +/- 9.3 mm Hg and 90.8 +/- 6.7 mm Hg and in controls from 158.2 +/- 16.5 mm Hg and 106.2 +/- 10.0 mm Hg to 136.3 +/- 10.8 mm Hg and 92.9 +/- 6.3 mm Hg (P < .0001 v baseline), respectively. Circadian BP rhythm in the study group returned to the normal profile (mean systolic nocturnal fall increased from 4.0% +/- 2.4% to 16.4% +/- 4.0% and diastolic, from 5.1% +/- 3.0% to 17.3% +/- 5.5%; P < .0001 v baseline), whereas it remained normal in the controls. CONCLUSIONS: Surgery-induced body weight loss in morbidly obese hypertensive subjects with impaired circadian BP variation is not only associated with BP reduction, but also with the restoration of normal BP rhythm.