Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

Functional Outcomes 18 Months After Total and Midarm Transplantation: A Case Report.

BACKGROUND: The function reported after arm transplantation is deemed beneficial relative to the marked disability that upper arm amputation causes. OBJECTIVE: We report a 51-year-old man with a Disabilities of the Arm, Shoulder and Hand (DASH) score of 75.83 who underwent bilateral arm transplantation in October 2015. PROCEDURE: The right arm was transplanted at the glenohumeral joint level, including transplantation of the humeral head, joint capsule, and rotator cuff ligaments and tendons. Additionally, neurorrhaphies were performed at the origin of the terminal branches of the brachial plexus, including the axillary and musculocutaneous nerves. Therefore, this was considered a total arm transplantation. The left arm was transplanted at the transhumeral level, with complete transplantation of the biceps and triceps brachii, and terminolateral neurorrhaphy of the donor musculocutaneous nerve to the receptor radial nerve. A maintenance triple immunosuppression scheme was administered, with tacrolimus levels kept at 10 ng/mL. RESULTS: At 18 months post-transplantation, the intrinsic musculature in the left hand showed electrical registry, DASH score was 67.5, Carroll test score was 28 in both extremities, Hand Transplant Score System was 67.5 in the right extremity and 77.5 in the left extremity, and Short Form-36 score was 96.1. The patient was healthy, with restored body integrity. He could lift medium-sized weightless objects, eat and go to the bathroom by himself, drink liquids with bimanual grasp, swim, dress almost independently, and drive. CONCLUSION: The functional evolution of the patient was similar to previously reported transplanted arms, even though the right arm transplant involved the glenohumeral joint and axillary and musculocutaneous nerve repair.

Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS). However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL) is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI). A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction. LEARNING POINTS: Pituitary infiltration by lymphoma can present with signs and symptoms of panhypopituitarism and diabetes insipidus.MRI findings can resemble an autoimmune hypophysitis.Patients can recover pituitary function as well as normalization of MRI after chemotherapy treatment.

Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human.

BACKGROUND: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. METHODS: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. RESULTS: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. CONCLUSIONS: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.

Association of the metabolic syndrome and long-term renal function in kidney donors.

BACKGROUND: Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors. METHODS: Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112). RESULTS: Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m(2) at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m(2) at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001) CONCLUSION: Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.

Laparoscopic adrenalectomy: lessons learned from an initial series of 100 patients.

BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard for the surgical treatment of adrenal disorders in most centers. This study analyzes the authors' experience using the lateral intraperitoneal approach with the first 100 patients. In addition to analyzing the authors' experience, this article aims to contrast it with some published series as an internal quality control. METHODS: In a 10-year period, 138 laparoscopic adrenalectomies were performed for 100 patients. Demographics, surgical results, complications, and long-term outcomes were analyzed. RESULTS: The participants comprised 69 women and 31 men with a mean age of 37 years. The procedures included 24 right, 38 left, and 38 bilateral adrenalectomies. The indications for surgery were Cushing's disease for 33 patients, pheochromocytoma (4 bilateral) for 23 patients, Cushing's syndrome for 18 patients, Conn's syndrome for 16 patients, and incidentaloma for 10 patients. Five procedures were converted to open surgery. Two patients with pheochromocytoma required intraoperative blood transfusion. The mean operative time was 174 min for unilateral adrenalectomies and 302 min for the bilateral procedures. The mean hospital stay was 5 days. Surgical morbidity included an abdominal wall hematoma, a small pneumothorax, and intraabominal bleeding in one patient that required reexploration. There were three operative mortalities not related to the technique. The long-term results showed control of hypercortisolism in all the patients with Cushing's disease and 82% of the patients with pheochromocytoma. Most of the patients with Conn's syndrome (91.4%) became normotensive after surgery. CONCLUSIONS: Laparoscopic adrenalectomy is safe and effective. The complications are mild, and mortality is related more to the patient's condition than to the surgical technique.

Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families.

Familial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1-2% in the general population. A major locus for FCHL has been mapped to chromosome 1q21-q23 in Finnish, Chinese, German and US families. We studied seven extended Mexican families with 153 members, including 64 affected subjects. A total of 11 markers were genotyped, including D1S104 which has been linked to FCHL in other studies. Two point linkage analysis for the FCHL phenotype, and for the elevated triglyceride (TG) trait, allowing for heterogeneity, gave a maximum HLOD of 1.67 (alpha = 0.49) and 1.93 (alpha = 0.43) at D1S2768 (2.69 cM proximal to D1S104) respectively. Heterogeneity and non-parametric (NPL) multipoint analyses for the FCHL phenotype and the TG trait showed maximum HLODs of 1.27 (alpha = 0.46) and 1.64 (alpha = 0.38), and NPLs of 4.00 (P = 0.0001) and 3.68 (P = 0.0003) near D1S2768, respectively. In addition, analysis of four candidate genes putatively involved in the expression of FCHL showed no evidence of linkage for the LCAT gene or the APOA1/C3/A4/A5 gene cluster. However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families. In conclusion, our data confirm the involvement of a major susceptibility locus on chromosome 1q21-q23 in FCHL Mexican families, consistent with findings in other populations.

The body mass index is a less-sensitive tool for detecting cases with obesity-associated co-morbidities in short stature subjects.

OBJECTIVE: To assess the ability of the body mass index (BMI) to detect obesity-associated morbidity in subjects with a normal or short stature. METHODS: Information was obtained on 119 975 subjects from a cardiovascular risk factors detection program. Standardized questionnaires were used. Capillary glucose and cholesterol concentrations were measured. Diabetes, arterial hypertension and hypercholesterolemia were selected as end points. Sensitivity, specificity and the likelihood ratio for several BMI thresholds were calculated. ROC curves were constructed to identify the BMI cutoff points with best diagnostic performance. The area under the curve (AUC) was used to assess the proficiency of BMI. RESULTS: Short stature (height

Insulin resistance and abdominal adiposity in young men with documented malnutrition during the first year of life.

OBJECTIVE: The main objective of the study was to examine the effect of early life malnutrition on the relation between insulin sensitivity and abdominal adiposity in adulthood. It was hypothesised that participants with early life malnutrition would display a more pronounced deterioration of insulin sensitivity in association with a gain in abdominal fat. DESIGN: As a first attempt to investigate this issue, we studied the effect of body fat gains in a cross-sectional context. SUBJECTS: A total of 26 young adult men with evidence of malnutrition during the first year of life and 27 control subjects were recruited for this study. Malnutrition status was determined from medical files of paediatric hospitals in the Mexico City metropolitan area. MEASUREMENTS: Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp, and body composition was measured by anthropometrics, bioelectrical impedance and computed tomography. RESULTS: There was a negative correlation between total abdominal adipose tissue area and insulin sensitivity in the previously malnourished and control groups (r(2)=0.65 and 0.35, P<0.01, respectively). When matched for low amounts of abdominal fat (114 cm(2)), participants with and without early life malnutrition had similar insulin sensitivity (9.03 vs 8.88 mg kg(-1) x min(-1)). However, when matched for high amounts of abdominal fat (310 cm(2)) participants who were malnourished during the first year of life had lower insulin sensitivity (4.74 vs 6.85 mg kg(-1) x min(-1), P<0.05). CONCLUSION: Higher levels of abdominal adipose tissue are more detrimental to insulin sensitivity in previously malnourished individuals.

The combination metformin/glyburide exerts its hypoglycemic effect mainly by increasing insulin secretion: a controlled, randomized, double-blind, crossover study.

The aim of the present study was to describe the mechanism by which the combination glyburide/metformin exerts its additive hypoglycemic effects. This is a double-blind, randomized and crossover clinical trial. Patients (n = 20) were included in a run-in period of 8 weeks in which an isocaloric diet was prescribed. If they did not achieve the treatment goals (n = 15), they received glyburide, metformin or combined treatment for 10 weeks each using three possible sequences. The dosage was adjusted to reach fasting plasma glucose (FPG) < 7.7 mmol/l. Treatment periods were separated by a 6-12 week washout period. At the beginning and the end of every treatment, insulin sensitivity and insulin secretion were measured by means of a minimal model and an oral glucose tolerance test. All treatment periods were completed by 12 cases. The glycemic goal was reached in 1 case during metformin, in 5 during glyburide and in 10 during the combination. The greatest reduction in HbA1c was achieved during the combination (HbA1c 11 +/- 1.6 vs 9.8 +/- 1.9 vs 9.0 +/- 2.1% for metformin, glyburide and the combination, p < 0.001). Increased insulin secretion was the explanation for the additive effects of the combination (percentual change in acute insulin response during the minimal model = 5.8 vs 51.5 vs 88.2% for metformin, glyburide and the combination, p < 0.05). No change in insulin sensitivity resulted from the treatments. In conclusion, the additive hypoglycemic effects of the combination glyburide/metformin was caused by increased insulin secretion.

Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.

OBJECTIVE: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. DESIGN: Double blind, parallel, prospective trial. METHODS: Forty-two male obese Zucker (falfa) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat (n = 14), placebo (n = 14) or fosinopril (n = 14) were administrated once daily at 10 micromol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. RESULTS: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group (p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116+/-9 vs 125+/-4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. CONCLUSIONS: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.

High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey.

The prevalence of lipid abnormalities revealed in a survey done in 417 Mexican cities is described. Information was obtained on 15,607 subjects, aged 20 to 69 years. In this report, only samples obtained after a 9- to 12-h fast were included (2,256 cases: 953 men and 1,303 women). The population is representative of Mexican urban adults. Mean lipid concentrations were: cholesterol, 4.80 mmol/l; triglycerides, 2.39 mmol/l; HDL cholesterol, 1.00 mmol/l; and LDL cholesterol, 3.06 mmol/l. The most prevalent abnormality was HDL cholesterol below 0.9 mmol/l (46.2% for men and 28.7% for women). Hypertriglyceridemia (>2.26 mmol/l) was the second most prevalent abnormality (24.3%). Severe hypertriglyceridemia (>11.2 mmol/l) was observed in 0.42% of the population. Increased LDL cholesterol (> or =4.21 mmol/l) was observed in 11.2% of the sample. Half of the hypertriglyceridemic subjects had a mixed dyslipidemia or low HDL cholesterol. More than 50% of the low HDL cholesterol cases were not related to hypertriglyceridemia. Insulin resistance was found in 59% of them. In conclusion, the prevalence of hypoalphalipoproteinemia and other forms of dyslipidemia in Mexican adults is very high and it is among the highest previously reported worldwide.

Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

Effects of estrogen/medrogestone therapy on the apoprotein B-containing lipoproteins in postmenopausal women with type 2 diabetes mellitus under satisfactory and non-satisfactory glycemic control.

BACKGROUND: Information is lacking on the effects of hormone replacement therapy in women with diabetes, especially during moderate chronic hyperglycemia. OBJECTIVES: To study the effects of HRT on the lipid profile and the low density lipoprotein subclass distribution in women with type 2 diabetes under satisfactory and non-satisfactory glycemic control. METHODS: Fifty-four postmenopausal women after a 6 week run-in diet were randomized to receive either placebo (HbA1c < 8%, n = 13; HbA1c > 8%, n = 17) or HRT (HbA1c < 8%, n = 11; HbA1c > 8%, n = 13) for 12 weeks. HRT consisted of cyclical conjugated estrogens 0.625 mg/day plus medrogestone 5 mg/day. At the beginning and at the end of each treatment period the LDL subclass distribution was estimated by density gradient ultracentrifugation. RESULTS: At the baseline and during the study, the HbA1c level was significantly higher in hyperglycemic patients than in the near-normoglycemic controls (baseline 10.2 +/- 2.9 vs. 6.5 +/- 0.7%, P < 0.01). They showed a trend for higher total and LDL cholesterol, triglycerides and lower high density lipoprotein-cholesterol compared to near-normoglycemic controls, as well as significantly higher triglyceride concentrations in very low density lipoprotein, intermediate density lipoprotein and LDL-1 particles and cholesterol content in LDL-1 and -2 particles. HRT decreased LDL-cholesterol in both groups. In the normoglycemic patients a small increase in HbA1c was observed (6.5 +/- 0.7 vs. 7.4 +/- 1%, P = 0.04). In all cases, HRT did not modify the proportion of LDL represented by denser LDLs. CONCLUSIONS: HRT did not modify the LDL subclass distribution, even in the presence of moderate chronic hyperglycemia in women with type 2 diabetes.

Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.

Lipids, apoprotein B, and associated coronary risk factors in urban and rural older Mexican populations.

The objective of this comparative cross-sectional study was to determine the prevalence of dyslipidemias and examine its association with food intake and metabolic variables in urban and rural elder Mexican populations. Three different communities (urban areas of medium and low income and a rural area) were studied. A total of 344 subjects aged 60 years and older and 273 aged 35 to 59 years were included. The evaluated parameters were personal medical data, 24-hour diet recall, and fasting plasma lipids, insulin, and glucose levels. Older subjects, especially men, living in the rural area had lower cholesterol levels (5.02 +/- 0.97 v 5.6 +/- 1.07 mmol/L; P <.05) and insulin levels (12 +/- 10 v 42 +/- 68 mU/mL) and higher high-density lipoprotein cholesterol concentrations (1.31 +/- 0.36 v 1.07 +/-0.28 mmol/L) than the elders from the urban medium-income group. Possible explanations for these differences are found in the dietary habits of the groups. Rural elders had higher amounts of fiber (20 +/- 11 v 10 +/- 6 g/d) and carbohydrate (70% +/- 0.08% v 52% +/- 0.11% of calories) and lower fat (18% +/- 0.07% v 33% +/- 0.1% of calories) in their diets. In the urban groups, low-density lipoprotein hypercholesterolemia was present in 17.8% of adult and 39.1% of elderly women (P =.00001). In conclusion, environmental factors still play a prominent role in the pathophysiology of the dyslipidemias in the elderly.

Comparing easy and accessible parameters of glycemic control in type 2 diabetes.

BACKGROUND: HbA1c is considered the gold standard of long-term glycemic control and is recommended as a routine test for every diabetic patient. However, its common use in clinical practice has some problems related to lack of standardization and its relative cost. Recent studies have suggested, that postprandial blood glucose could be better than a fasting sample, as a marker of diabetes control. The objective of the present study was to evaluate the relative value of plasma glucose samples at different times of the day, and easy and accessible programs for home blood and urinary glucose measurements compared with HbA1c in assessing the mean glycemic control of type 2 diabetic patients. METHODS: Sixty type 2 diabetic patients were instructed to do home blood and urine glucose monitoring for two months, at the end, plasma glucose profiles were obtained. RESULTS: The mean of all the capillary BG measurements had the best correlation with the HbA1c (r = 0.84, p < 0.001), followed by the mean of the capillary BG measurements before breakfast and supper (r = 0.82, p < 0.001), and the 2 hr. postbreakfast plasma glucose (r = 0.79 p < 0.001). The fasting PG had a low correlation (r = 0.65, p < 0.001), but a good sensitivity to predict a fair or a poor metabolic control. Diabetes duration and type of treatment explained 17% and 28% of variance in HbA1c levels. CONCLUSIONS: A bimonthly fasting PG correlated well with the glycosylated hemoglobin and is the easiest and cheapest way of monitoring glycemic control in type 2 diabetic patients with some preserved insulin reserve (diabetes for less than 10 years and on treatment with only one hypoglycemic agent). A sample of capillary BG, fasting, once per week correlates better with the HbA1c than a fasting PG every 2-3 months. The 2 hr and 5 hr postbreakfast PG have a good correlation with the HbA1c, but are not a substitute for doing BG monitoring. Glycosuria may be a useful parameter to rule out a fair or poor metabolic control in some patients.

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of

Leukocyturia in women with diabetes and its clinical implications.

BACKGROUND: Urinalysis is one of the most common studies performed on the diabetic patient at every visit. The presence of leukocyturia is relatively common but it is not clear what the attitude of the physician toward this particular finding should be. The main objective of the present study was to investigate the clinical significance of leukocyturia in diabetic women. METHODS: Ninety-eight diabetic women (84.7% type 2) aged 57 +/- 13 years who were being seen at the diabetic out-patient clinic were randomly selected. All patients underwent a clinical and gynecologic examination and a urinalysis. A Papanicolaou smear and a urine culture were also obtained. RESULTS: The overall prevalence of leukocyturia (>5 cells/high power field (hpf)) was 46.5%. Patients with urinary tract infections (UTI) were 7.5 times more likely to have leukocyturia, while a leukocyte count <5cells/hpf predicted the absence of UTI in 96% of the women. In the comparison of patients with and without leukocyturia, we found that proteinuria (p = 0.06) and bacteriuria (p <0.002) were more common in the women with leukocyturia. A significant association with leukorrhea was not demonstrated. The empirical use of antibiotics was 12 times more frequent in the patients with leukocyturia. CONCLUSIONS: A urinary culture should be requested in all diabetic patients with leukocyturia. The possibility of a UTI is remote when leukocyturia is absent.