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Biomedical subjects

Julio Wainstein

Publications and source records attributed to Julio Wainstein.

11 recordsLinked to original sources

PTHrP and insulin levels following oral glucose and calcium administration.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP), identified as a tumor product, is responsible for humoral malignant hypercalcemia. Unlike PTH, PTHrP is found in almost every body tissue including pancreatic alpha, beta, delta, and pp cells, where it is processed into multiple secretory forms, co-packaged with insulin, and secreted in a regulated fashion in response to insulin secretagogues. Ionized calcium is a stimulator for the release of several peptide hormones. METHODS: In the present study, we examined the effect of an oral calcium (1 g elemental calcium) and glucose (75 g) load on insulin and PTHrP release in 16 healthy volunteers and of an oral calcium load in 16 non-insulin-dependent diabetes mellitus (NIDDM) patients. Serum calcium, glucose, insulin, and PTHrP levels were determined at 0, 5, 10, 15, 30, and 60 min. RESULTS: Our results indicate that, at each time point, type 2 diabetic patients exhibited greater basal values of PTHrP than controls (200.3+/-110.5 pg/ml vs. 82.0+/-22.3 pg/ml, respectively, p<0.0001). The PTHrP level was consistently higher in response to the glucose load than the calcium load at each time point observed (p<0.0001). NIDDM patients exhibited greater basal serum PTHrP levels than the control group. CONCLUSION: PTHrP was proven for the first time to be released from beta cells in parallel to insulin and in response to glucose stimulation.

Journal Article↗

Adiponectin and the development of diabetes in patients with coronary artery disease and impaired fasting glucose.

OBJECTIVES: Adiponectin has insulin-sensitizing properties, and high adiponectin levels have been shown to be associated with reduced risk of developing diabetes. Patients with coronary artery disease (CAD) have relatively low adiponectin levels and high prevalence of glucose intolerance. The role of adiponectin in predicting the development of diabetes in this high-risk group has not been determined. The study aimed to determine whether baseline adiponectin levels predict the development of diabetes in a group of patients with CAD and impaired fasting glucose (IFG). METHODS: A total of 588 patients who participated in the Bezafibrate Infarction Prevention (BIP) study and who had at baseline fasting glucose of 100-125 mg/dl were included and followed for 6.2+/-1.3 years. Adiponectin was determined in frozen plasma samples taken at baseline. RESULTS: Of the patients with IFG at baseline, 256 (44%) developed diabetes during follow-up. The patients who developed diabetes had at baseline higher body-mass index, fasting glucose, C-reactive protein, triglycerides, homeostatic assessment of insulin resistance (HOMA-IR) and diastolic blood pressure than patients who did not develop diabetes. Adiponectin levels at baseline were significantly lower in patients who developed diabetes than in patients who did not develop diabetes (P = 0.009, nonparametric Kruskall-Wallis test). An increase of 1 unit of natural logarithm of adiponectin level was associated with a hazard ratio of 0.77 (95% CI, 0.61-0.96) for diabetes development. CONCLUSION: Patients with CAD and IFG have a very high rate of conversion to type 2 diabetes. Even in this high-risk group, high adiponectin levels are associated with reduced risk of developing diabetes.

Adiponectin↗

[The guidelines for the diagnosis prevention and treatment of type 2 diabetes mellitus--2005].

The incidence and prevalence of diabetes have reached epidemic proportions worldwide. The reasons for the pandemic are the sharp rise in obesity, decline in physical activity and the increase in life expectancy. There are some 400,000 people with diagnosed diabetes in Israel and they are at a markedly increased risk for cardiovascular disease, blindness, end-stage renal disease and lower limb amputation. To effectively lower this significantly increased burden of disease, a comprehensive multidisciplinary approach to chronic disease management is required. To facilitate such an approach, the Israel Diabetes Association published a guideline for the diagnosis, prevention and treatment of diabetes. The guideline, based on the ADA (American Diabetes Association) and IDF (International Diabetes Federation) guidelines, was approved by other national professional societies including hypertension, family practice, obesity, nephrology, atherosclerosis and internal medicine. The guidelines highlight the metabolic syndrome and prediabetic states, interventions for the prevention of diabetes, the new definitions of diabetes and impaired glucose metabolism and the newly defined targets for glucose, lipid, cholesterol and blood pressure control. In addition, the recommendations for periodic review and screening for complications are summarized. The need for patient education and empowerment are emphasized as is the need for the development and implementation of unique tools including computerized treatment flow-charts, prompts and quality measures, for the long term management of a complex metabolic disease.

Blood Glucose↗

Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men.

OBJECTIVE: Erectile dysfunction is frequently observed in diabetes. The current study aims to assess the association of a comprehensive set of clinical, socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic men. RESEARCH DESIGN AND METHODS: Participants were randomly selected from male patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants completed a self-reported questionnaire on demographic, socioeconomic, and lifestyle characteristics and on erectile function, using the IIEF-15 (International Index of Erectile Function). Information on diabetes type, duration, treatment, and control; microvascular complications and cardiovascular disease; drug therapy; blood pressure; and lipid levels was also obtained. RESULTS: Information on erectile function was obtained in 1,040 patients. Their mean age was 57 years, and their median diabetes duration was 8 years (range <1-50). Normal erectile function was found in 13.5% of the patients and severe erectile dysfunction in 30.1%. The characteristics found to be significantly associated with erectile dysfunction [associations presented as adjusted odds ratio (95% CI)] were: patient's age (5-year increments): 1.38 (1.29-1.48); diabetes duration (5-year increments): 1.16 (1.07-1.26); current HbA(1c) level (1% increment): 1.10 (1.01-1.19); any microvascular disease: 1.43 (1.09-1.88); cardiovascular disease: 1.78 (1.27-2.48); and diuretic treatment: 1.78 (1.09-2.91). Leisure time and work-related physical activity and consumption of small amounts of alcohol were found to be protective: 0.51 (0.36-0.72) and 0.70 (0.51-0.97), respectively. CONCLUSIONS: In diabetic men, erectile dysfunction severity increases with age and diabetes duration, poor glycemic control, presence of microvascular complications, diuretic treatment, and cardiovascular disease. Physical activity and alcohol intake may be protective. These findings can guide clinicians in taking preventive measures and undertaking early screening and treatment in high-risk patients.

Adult↗

[Primary care for type 2 diabetes].

The prevalence of type 2 diabetes is dramatically increasing worldwide and expected to double over the next 25 years, reaching epidemic proportions and thus incurring a considerable financial burden on the health care system. In order to cure the epidemic and minimize expensive complications, a program aimed at optimizing metabolic control and improving surveillance and quality assessment needs to be developed and implemented nation-wide. Most diabetic patients should be treated within the primary care system. In order to meet treatment targets, improve metabolic control and avoid complications, the knowledge and skills needed to treat this chronic disease should be reinforced by dedicated multidisciplinary teams from centers specializing in diabetes care. The specialized diabetes clinics should be devoted to both the treatment of complicated cases of diabetes, that are not achieving treatment targets in the primary care setting, and to the education, updating and empowerment of all primary care teams involved in the treatment of patients with diabetes. A local framework for shared care should be developed through the combined efforts, of the staff of the diabetes center and the primary care physicians and nurses in order to secure the shared goals of optimal treatment and prevention of complications.

Diabetes Mellitus, Type 2↗

Addition of biphasic insulin aspart 30 to rosiglitazone in type 2 diabetes mellitus that is poorly controlled with glibenclamide monotherapy.

BACKGROUND: The incidence of type 2 diabetes mellitus (DM) is rapidly increasing worldwide. Results from large-scale studies show that tight blood glucose (BG) control improves the outcome of patients with type 2 DM. OBJECTIVE: This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione (rosiglitazone [ROS]) to existing sulfonylurea (SU) therapy (glibenclamide) compared with switching to combination treatment with a premixed insulin (biphasic insulin aspart 30 [BIAsp 30], a rapid-acting insulin analog) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy. METHODS: In this 6-week, multicenter, open-label, parallel-group trial, patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy (glycosylated hemoglobin [HbA1c] 8%-13%) were randomized either to replace glibenclamide with BIAsp 30 (individually titrated dosages starting with 6-8 U BID) plus rosiglitazone (4 mg once daily) (BIAsp 30 + ROS group) or to add rosiglitazone (4 mg once daily) to their pretrial doses of glibenclamide (GLIB + ROS group). Patients measured their BG levels immediately before each of the 3 main meals, 90 minutes after the start of each meal, and at bedtime, and mean BG levels were calculated at weeks 0 (baseline), 1, 2, 4, 6, and at 2-week follow-up (week 8). The primary end point was change in mean daily BG level during treatment. Secondary end points included preprandial, postprandial, and bedtime BG levels, serum fructosamine level HbA, and fasting BG level, which were measured at each study visit. Tolerability was assessed using hematologic and biochemical parameters, vital signs, and physical examination. RESULTS: Forty-nine patients (32 men, 17 women; mean [SD] age, 59.1 [8.9] years; mean [SD] body mass index, 27.7 [3.7] kg/m2) participated in the study. A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 (P=0.01). After the 6-week treatment period, change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS (P=0.02). HbA1c decreased in both treatment groups from baseline to study end, but the difference between groups was nonsignificant. The changes in fasting BG from baseline to study end also were nonsignificant between groups. Both combinations were well tolerated. CONCLUSIONS: This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment. The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control.

Adult↗

Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus.

OBJECTIVE: The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus. METHODS: In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C- peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals. RESULTS: Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg x 100. Large artery elasticity tended to increase toward the end of the study (P = not significant). Systolic blood pressure (BP)decreased from 144 to 124 mm Hg and diastolic BP decreased from 80 to 62.5 mm Hg, despite mild weight gain [corrected]. Heart rate tended to decrease from 76.3 to 74.7 beats/min (P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm(5). Plasma insulin, in patients not treated with insulin, decreased from 42.45 +/- 24.90 to 27.86 +/- 14.86 IU/mL (P =.0001). CONCLUSIONS: Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.

Adult↗

Association of hyperglycemia and insulin with diabetic cardiovascular complications.

Patients with diabetes and/or insulin resistance syndrome are at increased risk for developing cardiovascular disease. The UKPDS raised a great debate about the relative importance of hyperglycemia in the development of cardiovascular disease. Recently, several epidemiologic studies have suggested that high postprandial blood glucose levels are associated with a significant risk for the development of cardiovascular disease well as a grave prognosis for these patients during acute coronary events. In addition, a number of reports reinforce the thesis that postprandial hyperglycemia is a risk factor for mortality. Our review summarizes the current knowledge on the relation between blood glucose, insulin levels, and cardiovascular morbidity and mortality, relating these data to the new World Health Organization and American Diabetes Association classification of disturbed glucose metabolism.

Blood Glucose↗

The effect of acarbose on the colonic transit time of elderly long-term care patients with type 2 diabetes mellitus.

BACKGROUND: Constipation is common in elderly patients with diabetes mellitus (DM); its prevalence is estimated as up to 60% among patients with diabetic neuropathy. Acarbose, an alpha-glucosidase inhibitor, has a beneficial role in controlling DM, although one of its side effects is diarrhea. This study evaluates the efficacy of acarbose in improving constipation using transit time (TT) studies in elderly long-term care (LTC) patients. METHODS: Twenty-eight patients with type 2 DM and constipation were recruited for the study. TT was measured by radiopaque markers and was calculated separately for the four segments of the colon (ascending, transverse, descending, and rectosigmoid) and for the total colonic transit time (CTT). Segmental TT and CTT were evaluated in each patient before and after 1 week, and again after 4 weeks of treatment with acarbose. RESULTS: The mean baseline CTT measured in patients was 202 plus minus 136 hours. After 1 and 4 weeks of acarbose treatment, the baseline CTT significantly decreased to 149 plus minus 107 hours and 161 plus minus 97 hours, respectively (p <.002). For each segment studied, the TT was shortened, but it reached significance for the ascending and transverse colon only (p <.02 and p <.03, respectively). The effect of diet composition was examined. The amount of fiber consumed correlated with shortened CTT, while fat tended to be in negative correlation with TT. CONCLUSIONS: Acarbose therapy reduced the extremely prolonged CTT in LTC diabetic persons with constipation. The drug could be useful in relieving constipation in these patients, in addition to its beneficial effect in the control of diabetes.

Acarbose↗

Reproducibility of glucose measurements using the glucose sensor.

OBJECTIVE: Recent studies have confirmed that improved glycemic control decreases the risk of diabetic complications in type 1 and type 2 diabetic patients. The Minimed glucose sensor allows continuous 72-h glucose monitoring and represents a potentially important tool to improve diabetes management. Its use is currently limited to the health care team. Our aim was to evaluate the reproducibility of data provided by the device by comparing data provided by two sensors worn simultaneously by the same subject. RESEARCH DESIGN AND METHODS: A total of 11 subjects (6 type 1 and 3 type 2 diabetic patients and 2 healthy subjects) agreed to wear two sensors and perform at least four daily finger-stick glucose determinations during 72 h. The simultaneous glucose values provided by the sensors were compared. To determine the clinical implications of the glucose data, each day was divided into eight periods, and for each period the glucose range was rated as satisfactory, too high, or too low by a blinded clinician experienced in interpreting glucose sensor data in the clinical setting. The evaluation of glycemic levels based on the recordings of the two sensors were compared for each paired time interval. RESULTS: We discarded 18% of the sensor data for technical reasons. Examined as a group, the remaining 3,370 paired data points in all 11 patients were highly correlated (r = 0.84). However, when individual pairs were evaluated, large differences in the glucose values were apparent, with differences of >10% in 70% of the measurements and >50% in 7% of the measurements. Moreover, clinical evaluation of the glucose range provided simultaneously by two sensors was concordant for only 65% of the evaluation periods. CONCLUSION: In a real-life setting, the accuracy of data provided by the Minimed glucose sensor may be less than expected. To avoid therapeutic errors, sensor findings should be confirmed by independent means before clinical decisions are made.

Blood Glucose↗