Tirzepatide Once Weekly for the Treatment of Obesity.

BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.

AIM: To assess the effect of tirzepatide on long-term risk of atherosclerotic cardiovascular disease (ASCVD) among people with obesity or overweight without diabetes from SURMOUNT-1. MATERIALS AND METHODS: SURMOUNT-1, a phase 3 trial, evaluated the efficacy and safety of tirzepatide in adults with body mass index ≥30 or ≥27 kg/m2 and at least one weight-related complication, excluding diabetes. Participants were randomly assigned to tirzepatide (5/10/15 mg) or placebo. Changes from baseline in cardiometabolic variables were assessed. The predicted 10-year ASCVD risk scores were calculated (American College of Cardiology/American Heart Association risk engine) at baseline, week 24, and week 72 in SURMOUNT-1 participants without a history of ASCVD. Percent change in risk scores from baseline to weeks 24 and 72 was compared between tirzepatide and placebo using mixed model for repeated measures analysis. Analyses were also conducted in participants with intermediate to high risk at baseline. RESULTS: Tirzepatide-treated groups demonstrated reductions in cardiometabolic variables over 72 weeks. In participants without a history of ASCVD (N = 2461), the baseline median risk score was low and did not differ across groups (1.5%-1.6%). Relative change in risk from baseline to week 72 was greater for tirzepatide (-23.5% to -16.4%) than placebo (12.7%; P < 0.001). Relative change among participants with intermediate-to-high baseline risk was significantly greater for tirzepatide (P < 0.05). Intermediate-to-high-risk participants demonstrated similar relative change but greater absolute risk reduction compared to the overall population. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of ASCVD versus placebo in patients with obesity or overweight without diabetes.

Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial.

AIM: We assessed the impact of tirzepatide on 10-year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT-1 trial. MATERIALS AND METHODS: In this post hoc analysis of SURMOUNT-1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10-year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline. RESULTS: Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%-24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%-20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%-11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo. CONCLUSION: Tirzepatide treatment significantly reduced the 10-year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.

Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.

AIM: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. RESULTS: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). CONCLUSIONS: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.

Critical phosphorus requirements of Trifolium species: The importance of root morphology and root acclimation in response to phosphorus stress.

Differences in root morphology and acclimation to low-phosphorus (P) soil were examined among eight legume species from the Trifolium Section Tricocephalum to understand how these root attributes determine P acquisition. Ornithopus sativus was included as a highly P-efficient benchmark species. Plants were grown as microswards in pots with five rates of P supplied in a topsoil layer to mimic uneven P distribution within a field soil profile. Topsoil and subsoil roots were harvested separately to enable measurement of the nutrient-foraging responses. Critical P requirement (lowest P supply for maximum yield) varied over a threefold range, reflecting differences in root morphology and acclimation of nutrient-foraging roots to P stress. Among the species, there was a 3.2-fold range in root length density, a 1.7-fold range in specific root length, and a 2.1-fold range in root hair length. O. sativus had the lowest critical P requirement, displayed a high root length density, the highest specific root length, and the longest root hairs. Acquisition of P from P-deficient soil was facilitated by development of a large root hair cylinder (i.e. a large root-soil interface). This, in turn, was determined by the intrinsic root morphology attributes of each genotype, and the plasticity of its root morphology response to internal P stress. Root acclimation in low-P soil by all species was mostly associated with preferential allocation of mass to nutrient-foraging roots. Only O. sativus and four of the Trifolium species adjusted specific root length beneficially, and only O. sativus increased its root hair length in low-P soil.

Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial.

BACKGROUND: Treating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups. METHODS: The mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis. RESULTS: Tirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group. CONCLUSIONS: In these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events. TRIAL REGISTRATION NUMBER: NCT04184622.

Health state utilities associated with weight loss in type 2 diabetes and obesity.

INTRODUCTION: Health state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D. METHODS: Health state vignettes were developed to represent respondents' own current weight and weight decreases of 2.5, 5, 10, 15, and 20%. Health state utilities were elicited in time trade-off interviews in two UK locations (Edinburgh and London) with a sample of participants with obesity, with and without T2D. Mean utility increases associated with each amount of weight decrease were calculated. Regression analyses were performed to derive a method for estimating utility change associated with weight decreases. RESULTS: Analyses were conducted with data from 405 individuals with obesity (202 with T2D, 203 without T2D). Utility increases associated with various levels of weight decrease ranged from 0.011 to 0.060 in the subgroup with T2D and 0.015 to 0.077 in the subgroup without T2D. All regression models found that the percentage of weight decrease was a highly significant predictor of change in utility (p < .0001). The relationship between weight change and utility change did not appear to be linear. Equations are recommended for estimating utility change based on the natural logarithm of percentage of weight decrease. DISCUSSION: Results of this study may be used to provide inputs for CUAs examining and comparing the value of treatments that are associated with substantial amounts of weight loss in patients with obesity, with or without T2D.

[Diabetes control in type 2 diabetic subjects treated in primary health care--how far is from life to standards?]. / Wyrównanie cukrzycy typu 2 u chorych pozostajacych pod wylaczna opieka lekarzy rodzinnych--jak daleko od zycia do standardów?

UNLABELLED: In Poland, as in many other countries, majority of type 2 diabetics subjects (80%) is treated by general practitioners (GPs). Aim of the study was to assess control of type 2 diabetic subjects treated by GPs in one of the big cities in Poland. Achievement of treatment goals was assessed according to recommendations of European Diabetes Policy Group (EDPG) published in 1998-1999 and used in Poland till 2004 and according to more rigorous criteria recommended in 2005 by Polish Diabetological Association (PDA). Study was conducted in 2004 year in 355 consecutive type 2 diabetic subjects coming for a visit to GPs in one of the primary health care centries. Group consisted of 205 women and 150 men, mean age 65.7 +/- 10.3 years, mean diabetes duration 9.2 +/- 7.3 years, mean BMI 29.9 +/- 4.9 kg/m2. In all patients blood pressure measurements were performed in sitting position and blood samples for HbA1c, fasting glycaemia, total cholesterol, LDL, HDL and triglicerides were taken. Mean HbA1c was 7.2 +/- 1.3%; HbA1c < or = 6.5% recommended by EDPG was found in 34,6% of patients, HbA1c < or = 6.1% recommended by PDA was achieved in 19.7% of subjects. Mean fasting glycaemia was 144 +/- 48 mg/dl; glycaemia < or = 110 mg/dl recommended by EDPG and PDA was present in 24% of patients. Dyslipidaemia was present in 62% of diabetics. Mean total cholesterol was 203.7 +/- 45 mg/dl, LDL 118 +/- 33 mg/dl, HDL 51 +/- 13 mg/dl. LDL cholesterol < 100 mg/dl recommended by EDPG and PDA was observed in 28.7% of subjects. HDL cholesterol > 46 mg/dl (EDPG criteria) was found in 61% of patients. HDL cholesterol > 40 mg/dl in men and > 50 mg/dl in women ( PDA criteria) was present 64.5% of subjects. Mean triglycerides level was 182 +/- 108 mg/dl; concentrations < 150 mg/dl (EDPG and PTD criteria) were observed in 46.2% of subjects. Hypertension was present in 81.4% of patients. Mean systolic blood pressure (SPB) was 146.1 +/- 20.4 mmHg, diastolic (DBP) 83.0 +/- 11.1 mmHg. Recommended by EDPG, SPB < 140 mmHg was observed in 47,9%, DBP < 85 mmHg--in 69.9%. Recommended by PTD, SBP < 130 mmHg was found in 16.1%, DBP < 80 mmHg--in 24.5%, and both values only in 8.2% of diabetics. All treatment goals recommended by EDPG-1998-1999 were achieved only in 2 patients. No one person achieved all goals of treatment recommended by PDA-2005. CONCLUSIONS: Great majority of type 2 diabetic subjects treated in primary health care failed to attain treatment goals recommended by EDPG 1998-1999 and by PDA 2005.

Lack of association between the Pro12Ala polymorphism in PPAR-gamma2 gene and body weight changes, insulin resistance and chronic diabetic complications in obese patients with type 2 diabetes.

BACKGROUND: It is generally accepted that the Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with an increased risk of type 2 diabetes. However, studies on an association between the polymorphism and obesity have yielded inconsistent findings. Also, a role of PPAR-gamma receptors in development of chronic diabetic complications cannot be excluded. The aim of this study was to investigate an association between Pro12Ala polymorphism and body weight changes, insulin resistance, insulin secretion and incidence of diabetic complications in obese patients with long-lasting type 2 diabetes. METHODS: In 216 obese patients with at least a 10-year history of type 2 diabetes, a detailed medical history was taken and a physical examination with assessment of diabetic complications was performed as well as evaluation of insulin resistance (homeostatic model assessment-HOMA), insulin secretion and other biochemical parameters. PCR-RFLP was used to assess Pro12Ala polymorphism. Two subgroups of patients were compared: homozygotic Pro/Pro and Ala allele carriers (Ala/Ala + Ala/Pro). RESULTS: No differences between the analyzed groups in body weight changes, insulin resistance and insulin secretion were found, but Ala allele was significantly more frequent in males than in females. There was no difference in incidence and progression of diabetic complications with only a trend towards higher incidence of diabetic retinopathy in patients with Ala allele. CONCLUSIONS: There is no association between Pro12Ala PPAR-gamma2 polymorphism and body mass changes observed during a course of type 2 diabetes, differences in peripheral insulin resistance and incidence and progression of diabetic complications in obese patients with long-lasting type 2 diabetes.

Root morphological traits that determine phosphorus-acquisition efficiency and critical external phosphorus requirement in pasture species.

Annual pasture legume species can vary more than 3-fold in their critical external phosphorus (P) requirement (i.e. P required for 90% of maximum yield). In this work we investigated the link between root morphology, P acquisition and critical external P requirement among pasture species. The root morphology acclimation of five annual pasture legumes and one grass species to low soil P availability was assessed in a controlled-environment study. The critical external P requirement of the species was low (Dactylis glomerata L., Ornithopus compressus L., Ornithopus sativus Brot.), intermediate (Biserrula pelecinus L., Trifolium hirtum All.) or high (Trifolium subterraneum L.). Root hair cylinder volumes (a function of root length, root hair length and average root diameter) were estimated in order to assess soil exploration and its impact on P uptake. Most species increased soil exploration in response to rates of P supply near or below their critical external P requirement. The legumes differed in how they achieved their maximum root hair cylinder volume. The main variables were high root length density, long root hairs and/or high specific root length. However, total P uptake per unit surface area of the root hair cylinder was similar for all species at rates of P supply below critical P. Species that maximised soil exploration by root morphology acclimation were able to prolong access to P in moderately P-deficient soil. However, among the species studied, it was those with an intrinsic capacity for a high root-hair-cylinder surface area (i.e. long roots and long root hairs) that achieved the lowest critical P requirement.

[Prevalence of diabetes, antidiabetic treatment and chronic diabetic complications reported by general practitioners]. / Ocena czestosci wystepowania cukrzycy, sposobu jej leczenia oraz czestosci powiklan o typie mikroangiopatii u osób pozostajacych pod opieka lekarzy podstawowej opieki zdrowotnej.

INTRODUCTION: Prevalence of type 2 diabetes has increased greatly over the past decade and focus of care for people with diabetes has shifted from specialists to general practitioners (GPs). Because of lack of the central registry, a real number of diagnosed diabetes in Poland is unknown, as unknown is the prevalence of diabetes in patients attending primary health care, provided treatment and a prevalence of chronic diabetic complications registered by GPs. AIM OF STUDY: Assessment of the prevalence of diabetes registered in primary health care, recommended antidiabetic treatment and prevalence of microangiopathic diabetic complications diagnosed by GPs. MATERIAL AND METHODS: Study was performed in Szczecin, a city of 450 000 inhabitants, located in North-West part of Poland. Data were obtained in year 2002 from one of the primary health care centers, in which health care was provided by 12 GPs for 27 932 inhabitants (15655 females and 12277 males), aged 0-98 years (average 38.3 +/- 23.2 years). Data were extracted from medical records and provided by GP doctors. RESULTS: Number of diagnosed and registered diabetics was 993 (prevalence--3.56%), age 3-95 years (mean 65.4 +/- 13.6 years). The diabetic group consisted of 611 females (mean age 67.5 +/- 12.4)--prevalence--3.90% and 382 males (mean age 62.0 +/- 14.7)--prevalence--3.11% (p = 0.003). Mean duration of diabetes was 7.4 +/- 6.9 years and it was similar for males and females. Type 2 diabetes was diagnosed in 94.4%, type 1 diabetes in 4.5%, other types of diabetes in 1.1% of all patients. Prevalence of registered diabetes in the group of 0-10 years old was 0.08%, in the group 11-20 years--0.33%, 21-30 years--0.25%, 31-40 years--0.44%, 41-50 years--1.93%, 51-60 years--5.03%, 61-70 years--9.88% and in the group over 70 years old--14.37%. Prevalence of diabetes in the group over 14 years old was 4.38%, in the group over 20 years--4.86%, and in subjects older than 35 years--6.84%. Elderly patients, over 60 years account for 74% of all diabetic subjects and subjects over 70 years--for 45% of them. Reported treatment of type 2 diabetes: diet alone--9%, oral agents--68%, oral agents combined with insulin--10.5%, insulin alone--12.5%. Mean HbA1c value measured in 307 type 2 diabetic subjects was 7.25 +/- 1.28%. According to GPs' opinion chronic microangiopathic diabetes complications were present in 36.6% of type 2 diabetic subjects. Retinopathy was reported in 24.8% of patients, polyneuropathy in 2.4%, nephropathy in 1.5%, diabetic foot in 0.5%, and combination of different complications in 7.4% of them. In type 1 diabetes chronic diabetic complications were stated in 42.2% of subjects--retinopathy--in 15.6%, polyneuropathy--in 2.2%, nephropathy--in 2.2%, diabetic foot--in 2.2%, and combination of them--in 20.0%. Average number of registered diabetics was 83 per physician, however 6 doctors took care of 107-158 diabetic subjects. In the past year diabetologist consultation or hospitalisation in internal medicine unit was provided for 47% of type 2 diabetics and for 98% of type 1 diabetics. CONCLUSIONS: 1. The prevalence of diabetes registered in primary health care in Szczecin is higher than expected on the basis of European data. 2. Low number of type 2 diabetics is treated with diet alone and quite high number is treated with insulin. 3. Low number of chronic diabetic complications reported by GPs, despite long duration of disease, indicates the necessity of special training in delivering care for diabetic people, diagnosis of diabetic complications, increased access to secondary care and better cooperation between primary and secondary care.

[Type 1 diabetes as a mask of a neuroendocrine tumour of pancreas]. / Cukrzyca typu 1 jako maska neuroendokrynnego guza trzustki.

Neuroendocrine tumours of pancreas originating from pancreatic islet cells are uncommon neoplasms with clinical manifestation depending on a type of hormone secreted. Diabetes as a clinical sign of such a tumour has been reported many times and is not an uncommon finding but it is generally mild and makes only a part ofa whole pattern of symptoms. We report on a case of a malignant neuroendocrine pancreatic tumour in 19 years old patient, where diabetes, with a clinical course typical for type 1 diabetes, was the first and the main symptom of the disease.

False diagnosis of type 1 diabetes mellitus and its complications in Wolfram syndrome--is it the reason for the low number of reported cases of this abnormality?

Wolfram syndrome (WS), also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness), is a rare autosomal recessive syndrome (1/770,000 in the United Kingdom), characterised by juvenile onset of diabetes mellitus, optic nerve atrophy, diabetes insipidus, sensorineural deafness, renal tract and neurological abnormalities, and primary gonadal atrophy. WS is caused mainly by biallelic mutations in the WFS1 gene, which encodes wolframin. Wide tissue distribution of wolframin and many mutations in the wolframin gene resulting in Wolfram syndrome may contribute to different phenotypes and the unusual combinations of clinical features. We describe a female patient with Wolfram syndrome diagnosed at the age of 25, with a previous false diagnosis of type 1 diabetes mellitus and misdiagnosed diabetic complications. The patient was found to be a compound heterozygote for two novel mutations in exon 8 of WFS1 gene: a 2-bp deletion AT at nt 1539 leading to a frameshift (Y513fs) and a single-base substitution 1174C > T resulting in a stop codon (Q392X). A detailed analysis of the patient's medical history and a review of the literature suggest that many cases of Wolfram syndrome may remain undiagnosed due to misdiagnosis as type 1 diabetes mellitus and incorrect interpretation of clinical symptoms of neurodegenerative abnormalities, especially in their early stages.

The common C49620T polymorphism in the sulfonylurea receptor gene SUR1 (ABCC8) in patients with gestational diabetes and subsequent glucose metabolism abnormalities.

AIM: The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism, ß-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM). MATERIAL AND METHODS: Study group included 199 women, diagnosed GDM within the last 5-12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) and ß-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined. RESULTS: The distribution of the studied polymorphism in the two groups did not differ from each other (χ(2) = 0.34, P = 0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ(2) = 7,13, P = 0, 3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR. CONCLUSIONS: The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population.

Diabetes care and self-monitoring of type 2 diabetic patients in a rural district of West-Pomeranian Province.

INTRODUCTION: Few surveys conducted in diabetic patients from rural regions show that in these subjects monitoring of diabetes is worse than in patients from urban areas. OBJECTIVES: To assess methods of diabetes care provided for type 2 diabetic patients residing in a rural region and methods of the patient self-monitoring of glycemia, blood pressure and foot self-care. PATIENTS AND METHODS: The survey was conducted in a rural district of West-Pomeranian province, in the primary health care center, where 279 type 2 diabetic patients were registered. Out of all patients invited to participate in a questionnaire survey, 168 were enrolled. The mean age of subjects was 67.2 +/- 9.9 years (range 46-91 years), diabetes duration of 8.2 +/- 6.6 years, and body mass index of 32.6 +/- 6.3 kg/m2. Data concerning diabetes care and methods of the patient self-control of glycemia, blood pressure and foot self-care were collected. RESULTS: The majority of patients (62%) were treated only by general practitioners, but 80% reported that they visited their doctors for diabetes treatment once a month. For 90% of subjects the term ,HbA1c" was unknown. Only 40% of patients performed self-monitoring of glycemia, 55%--of blood pressure and 34% examined their feet. CONCLUSIONS: The vast majority of patients from a rural region in West-Pomeranian province is treated only by general practitioners. Despite quite frequent medical visits related to diabetes, education of patients is still unsatisfactory, which was demonstrated by patients' lack of knowledge concerning the basic parameter of laboratory monitoring, HbA1c, as well as insufficient self-management of glycemia, blood pressure and infrequent foot exam.

[Diabetes control in type 2 diabetic subjects treated in primary health care]. / Wyrównanie cukrzycy typu 2 u chorych leczonych przez lekarzy podstawowej opieki zdrowotnej.

Aim of the study was to assess control of type 2 diabetes in subjects treated by general practitioners. Study was conducted in one of the primary health care centers in a big city, in which health care was provided for 27 900 inhabitants. Control of diabetes was assessed in 355 of all 936 type 2 diabetic subjects registered in the center. None of them was seen by diabetologist in the preceeding year. Mean age was 65,7 +/- 10,3 lat, diabetes duration 9,2 +/- 7,3 lat, BMI 29,9 +/- 4,9 kg/m2. Normal body weight was found in 15%, overweight in 39%, obesity in 46% of subjects. Hypertension was present in 81%, dyslipidaemia in 62% of patients. Mean HbAlc was 7,2 +/- 1,3%, fasting serum glycaemia 144 +/- 48 mg/dl, total cholesterol 204 +/- 45 mg/dL, LDL - 119 +/- 33 mg/dL, HDL - 51 +/- 13 mg/dl, triglicerides 182 +/- 108 mg/dL. Mean systolic blood pressure was 146 +/- 20 mmHg, diastolic 83 +/- 11 mmHg. Treatment goals recommended by Polish Diabetological Association in 2005 were attained as follows: HbAlc < or = 6,1% - 19,7% of subjects, fasting glycaemia < or =110 mg/dl - 24%, total cholesterol < 175 mg/dl - 26%, LDL < 100 mg/dl - 29%, triglicerides < 150 mg/dl - 46%, cholesterol HDL > 40 mg/dl in men and > 50 mg/dl in women - 65% of subjects. Recommended systolic blood pressure < 130 mmHg was found in 16 %, diastolic blood pressure < 80 mmHg - in 24%, and both values - in 8% of diabetics. In no one subject all recommended treatment goals were met. Conclusions 1. Recommended treatment goals are perceived in unacceptably low number of type 2 diabetic subjects treated by general practitioners. 2. Medical care of type 2 diabetic subjects performed in primary health care is unsatisfactory and should be essentially improved or changed.

Regression of renal vascular and glomerular fibrosis: role of angiotensin II receptor antagonism and matrix metalloproteinases.

Renal fibrosis is one of the major complications associated with the development of hypertension. The objective of the present study was to determine whether and by which mechanisms treatment with AT1 receptor antagonists makes possible the regression of renal vascular and glomerular fibrosis. Experiments were performed in the hypertensive model of nitric oxide (NO) deficiency in rats. After 4 wk of hypertension, mortality rates averaged 20%; the surviving animals displayed a decline of renal function (urine protein/creatinine, 1.89 +/- 0.63 versus 0.24 +/- 0.03 mg/mmol; creatininemia, 110 +/- 14 versus 38 +/- 2 mmol/L in hypertensive animals and control, respectively; P < 0.01) and an exaggerated gene and protein expression of TGF-beta, collagen I, and collagen IV (P < 0.001) within the renal vasculature associated with the development of glomerulosclerosis (sclerotic index, 2.26 +/- 0.29 versus 0.12 +/- 0.04; P < 0.001). In addition, activities of matrix metalloproteinases 2 and 9 were increased twofold in renal vessels and glomeruli (P < 0.01). Afterwards, losartan, an antagonist of angiotensin receptor type I, or hydralazine were administered in subgroups of hypertensive animals. After 1 wk of angiotensin II antagonism, collagen I, collagen IV, and TGF-beta gene and protein expressions were decreased and glomerulosclerosis was less marked (sclerotic index 1.04 +/- 0.45), whereas activities of metalloproteinases remained twofold higher than controls (P < 0.01). Hydralazine failed to improve renal function despite a similar degree of systolic pressure decrease. After 4 wk of losartan, the renal functional and histologic parameters were completely normalized, whereas they remained damaged in the hypertensive animals in which the mortality rate reached 85%. These data suggest that the progression of renal vascular fibrosis is a reversible process, at least in the NO deficiency model. The mechanism of the regression appears to be dual: inhibition of collagen synthesis due to AT1 receptor antagonism and activation of metalloproteinases that is probably associated with the degree of fibrosis independently of AT1 blockade.