The triglycerides and glucose index is more strongly associated with metabolically healthy obesity phenotype than the lipid and obesity indices.

PURPOSE: The triglycerides and glucose (TyG) index is a reliable biomarker for estimating insulin resistance; however, evidence regarding the use of the TyG index in individuals with metabolically healthy obesity (MHO) is scarce. Thus, we examined the association between the TyG index and the MHO phenotype. METHODS: Apparently healthy men and women aged 18 years or more with obesity (body mass index [BMI] ≥ 30 kg/m2) were allocated into the following groups: MHO and metabolically unhealthy obesity (MUO). The MHO phenotype was defined by obesity and the absence of the following metabolic disorders: elevated triglyceride concentrations, elevated glucose levels, elevated blood pressure, and low HDL-C. The MUO was defined by individuals with obesity and at least one of the aforementioned cardiovascular risk factors. RESULTS: A total 827 individuals, 605 (73.1%) women and 222 (26.9%) men were enrolled and allocated into the MHO (n = 104) and MUO (n = 723) groups. The adjusted regression analysis by age, sex, BMI, and waist circumference showed that fasting glucose (OR = 0.90; 95% CI: 0.88-0.93), and triglycerides (OR = 0.97; 95% CI: 0.96-0.98), as well as the triglycerides/HDL-C (OR = 0.18; 95% CI: 0.13-0.26), lipid accumulation product (OR = 0.95; 95% CI: 0.93-0.96), visceral adipose index (OR = 0.38; 95% CI: 0.31-0.46), and TyG index (OR = 0.001; 95% CI: 0.000-0.004) are inversely associated with the MHO, while the HDL-C (OR = 1.10; 95% CI: 1.07-1.12) had a direct association. CONCLUSIONS: Our results show that the TyG index is more strongly associated with the MHO phenotype than the lipid and obesity indices.

The triglycerides and glucose index is associated with cardiovascular risk factors in metabolically obese normal-weight subjects.

PURPOSE: The aim of this study was to determine whether the triglycerides and glucose (TyG) index is associated with the presence of metabolically obese normal-weight (MONW) phenotype and related cardiovascular risk factors. METHODS: Apparently healthy men and non-pregnant women aged 20-65 years were enrolled in a population-based cross-sectional study. Overweight, obesity, smoking, alcohol consumption, pregnancy, diagnosis of hypertension, diabetes, cardiovascular disease, liver disease, renal disease, malignancy, and medical treatment were exclusion criteria. Subjects were allocated into the MONW or normal-weight groups. MONW phenotype was defined by normal weight and the presence of at least one of the following cardiovascular risk factors: elevated blood pressure, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol. RESULTS: A total of 542 subjects were enrolled and allocated into the MONW (n = 354) and normal-weight (n = 188) groups. The adjusted logistic regression analysis showed that the elevated TyG index is significantly associated with the presence of MONW phenotype (OR = 11.14; 95% CI 6.04-20.57), hyperglycemia (OR = 3.18; 95% CI 1.95-5.21), hypertriglyceridemia (OR = 399.19; 95% CI 94.01-1694.98), and low HDL-C (OR = 2.60; 95% CI 1.74-3.87), but not with elevated blood pressure (OR = 1.55; 95% CI 0.93-2.60). CONCLUSION: Results of this study support that the TyG index may be a useful indicator to detect MONW phenotype and associated cardiovascular risk factors.

The triglyceride and glucose index is useful for recognising insulin resistance in children.

AIM: Although recognising insulin resistance (IR) in children is particularly important, the gold standard test used to diagnose it, the euglyceamic glucose clamp, is costly, invasive and is not routinely available in our clinical settings in Mexico. This study evaluated whether the triglyceride-glucose (TyG) index would provide a useful alternative. METHODS: A total of 2779 school children aged seven to 17 years, from Durango, Mexico, were enrolled during 2015-2016. The gold standard euglyceamic-hyperinsulinemic clamp test was performed in a randomly selected subsample of 125 children, and diagnostic concordance between the TyG index and the homoeostasis model assessment of IR was evaluated in all of the 2779 enrolled children. RESULTS: The best cut-off values for recognising IR using the TyG index were 4.65 for prepubertal girls and boys, 4.75 for pubertal girls and 4.70 for pubertal boys. Concordance between the TyG index and the homoeostasis model assessment of IR was 0.910 and 0.902 for the prepubertal girls and boys, 0.932 for the pubertal girls and 0.925 for the pubertal boys. CONCLUSION: The TyG index was useful for recognising IR in both prepubertal and pubertal children and could provide a feasible alternative to the costly and invasive gold standard test for IR in resource-limited settings.

BORIS and CTCF are overexpressed in squamous intraepithelial lesions and cervical cancer.

We investigated the expression of Brother of Regulator of Imprinted Sites (BORIS) and CCCTC-binding factor (CTCF) in squamous intraepithelial lesions and cervical cancer. To analyze BORIS and CTCF expression, an endocervical cytobrush sample was taken for total RNA isolation. CTCF and BORIS mRNA was quantified from total RNA using quantitative reverse transcription-polymerase chain reaction. A total of 71 samples were collected and classified according to the Bethesda Classification of squamous intraepithelial lesions. BORIS expression was observed in 9 (12.7%) samples; of these, 5.3, 5.9, 14.8, and 37.5% in the groups that were cytology negative for intraepithelial lesion or malignancy, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical carcinoma, respectively. The expression level of BORIS was significantly higher in the group with invasive cervical carcinoma as compared with the groups negative for intraepithelial lesion or malignancy, LSIL, and HSIL (P < 0.0005). CTCF mRNA was expressed in all samples. CTCF expression was significantly higher in carcinoma groups compared with LSIL, HSIL, and negative for intraepithelial lesion or malignancy groups. We found that BORIS and CTCF expressions in the LSIL and invasive cervical carcinoma groups were higher than expression in cytological normal samples. Additional studies should be conducted to examine the function of transcription factors during different stages of the transformation of cervical cancer cells.

Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta-analysis of clinical trials.

AIMS: To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta-analysis of clinical trials. METHODS: A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using an unrestricted maximum likelihood method to evaluate the association between statin-induced elevation of plasma PCSK9 concentrations with duration of treatment and magnitude of LDL cholesterol reduction. RESULTS: A total of 15 clinical trials examining the effects of statin therapy on plasma PCSK9 levels were included. Meta-analysis of data from single-arm statin treatment arms [weighted mean difference (WMD) 40.72 ng/ml, 95% confidence interval (CI) 34.79, 46.65; p < 0.001] and randomized placebo-controlled trials (WMD 22.98 ng/ml, 95% CI 17.95, 28.01; p < 0.001) showed a significant increase in plasma PCSK9 concentrations after statin therapy, irrespective of the type of statin administered in either of the analyses (single-arm or randomized placebo-controlled trial). There was no significant elevation of plasma PCSK9 levels with statin/ezetimibe combination therapy compared with statin monotherapy (WMD 23.14 ng/ml, 95% CI -1.97, 48.25; p = 0.071); however, removal of one study in the meta-analysis yielded a significant result in the sensitivity analysis (WMD 31.41 ng/ml, 95% CI 7.86, 54.97; p = 0.009). CONCLUSIONS: This meta-analysis suggests that statin therapy causes a significant increase in plasma PCSK9 concentrations.

Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial.

AIM: This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia. METHODS: A total of 116 men and non-pregnant women, aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes, were enrolled into a randomized double-blind placebo-controlled trial to receive either 30 mL of MgCl2 5% solution (equivalent to 382 mg of magnesium) or an inert placebo solution once daily for four months. The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels. RESULTS: At baseline, there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups. At the end of follow-up, fasting (86.9 ± 7.9 and 98.3 ± 4.6 mg/dL, respectively; P = 0.004) and post-load glucose (124.7 ± 33.4 and 136.7 ± 23.9 mg/dL, respectively; P = 0.03) levels, HOMA-IR indices (2.85 ± 1.0 and 4.1 ± 2.7, respectively; P = 0.04) and triglycerides (166.4 ± 90.6 and 227.0 ± 89.7, respectively; P = 0.009) were significantly decreased, whereas HDL cholesterol (45.6 ± 10.9 and 46.8 ± 9.2 mg/dL, respectively; P = 0.04) and serum magnesium (1.96 ± 0.27 and 1.60 ± 0.26 mg/dL, respectively; P = 0.005) levels were significantly increased in those taking MgCl2 compared with the controls. A total of 34 (29.4%) people improved their glucose status (50.8% and 7.0% in the magnesium and placebo groups, respectively; P < 0.0005). CONCLUSION: Our results show that magnesium supplementation reduces plasma glucose levels, and improves the glycaemic status of adults with prediabetes and hypomagnesaemia.

Tumor necrosis factor haplotype diversity in Mestizo and native populations of Mexico.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

Aggravation by vanadium of magnesium deficiency in STZ-induced diabetic rats.

This study examined changes in the metabolism of magnesium (Mg), and related serum parameters, following treatment with vanadium (V) in streptozotocin-diabetic rats. Over a period of five weeks, four groups were examined: control, diabetic, diabetic-treated with 1 mg V/day or 3 mg V/day. The V was supplied in drinking water as bis(maltolato)oxovanadium(IV). The Mg levels were measured in food, faeces, urine, serum, muscle, kidney, liver, spleen, heart and femur. Albumin, uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides, aspartate-aminotransferase and alkaline-phosphatase were determined in serum. In the diabetic group, Mg retained and Mg content in serum and femur decreased, while levels of uric acid, urea, total-cholesterol, LDL-cholesterol, triglycerides and alkaline-phosphatase and aspartate-aminotransferase activity increased compared with control rats. In the diabetic group treated with 1 mg V/day, Mg retained, serum levels of Mg, urea and triglycerides, and alkaline-phosphatase activity remained unchanged, while levels of uric acid, total-cholesterol and LDL-cholesterol increased and the Mg content in femur and aspartate-aminotransferase activity decreased compared with the diabetic untreated group. In the diabetic rats treated with 3 mg V/day, food intake and glycaemia were normal. In this group, Mg content in serum, kidney and femur, levels of urea and aspartate-aminotransferase and alkaline-phosphatase activity decreased, whereas LDL-cholesterol increased, uric acid and total-cholesterol levels remained unchanged in comparison with untreated diabetic rats. In conclusion, although treatment with 3 mg V/day normalised the glycaemia, the hypomagnesaemia and tissue depletion of Mg seen in the diabetic rats, caused by the treatment with V, could have partially contributed to the fact that V did not normalise other serum parameters altered by the diabetes.

Dietary factors related to the increase of cardiovascular risk factors in traditional Tepehuanos communities from Mexico. A 10 year follow-up study.

BACKGROUND AND AIMS: Tepehuanos Indians, a traditional Mexican ethnic group, followed a vegetarian diet exhibiting a low prevalence of obesity and the absence of diabetes. However, from the year 2000 the traditional diet of the Tepehuanos was modified by the introduction of western food. In this study we examine the changes in their customary diet and its impact on the prevalence of cardiovascular risk factors in this group. METHODS AND RESULTS: Individuals from 12 Tepehuanos communities were randomly enrolled during 1995-1996 and 2006-2007. Using a 64-item semiquantitative food frequency questionnaire macronutrient intakes were calculated from values of Mexican food-composition tables. Cardiovascular risk factors such as obesity, hypertension, hyperglycemia and dyslipidemia were determined. The median (25, 75 percentile) of total caloric intake (1476 [1083, 1842]-2100 [1366, 2680]kcal/day, p<0.001) as well as the percentage of energy consumed from saturated fat (3.0 [2.7,4.1]-7.2 [3.9,7.4], p<0.0001) and protein (8.2 [7.8,8.9]-16.8 [16.3,17.1], p<0.0001) increased, whereas the percentage of total calorie intake from carbohydrates (66.4 [61.3,69.5]-61.3 [61,68.8], p<0.0001), polyunsaturated fat (11.2 [10.3,12.1]-4.0 [3.9,4.3], p<0.0001), and the polyunsaturated:saturated fat ratio (3.84-0.53%, p<0.0001) decreased during the period of study. The prevalence of obesity (11.1-21.9%, p=0.04), impaired fasting glucose (5.9-14.9%, p=0.04), diabetes (0.0-0.88%, p=0.48), hypertension (1.7-3.4%, p=0.43), triglycerides (2.6-16.7%, p=0.0006), and low HDL-cholesterol (10.2-71.1%, p<0.0001) increased. CONCLUSIONS: Changes in the customary diet introduced in the Tepehuanos communities are related to the increase of cardiovascular risk factors.

The effect of lowering blood pressure by magnesium supplementation in diabetic hypertensive adults with low serum magnesium levels: a randomized, double-blind, placebo-controlled clinical trial.

To test the blood pressure (BP)-lowering effect of oral magnesium supplementation (that is, magnesium chloride (MgCl(2)) solution) in diabetic hypertensive adults with hypomagnesaemia not on diuretic treatment but receiving concurrent captopril, we conducted a double-blind, placebo-controlled trial. Eighty-two subjects between 40 and 75 years of age were randomly enrolled. Over 4 months, subjects in the intervention group received 2.5 g of MgCl(2) (50 ml of a solution containing 50 g of MgCl(2) per 1000 ml of solution) equivalent to 450 mg of elemental magnesium, and control subjects inert placebo. The primary trial end point was a reduction in systolic (SBP) and diastolic (DBP) blood pressure. Complete follow-up was achieved for 79 of the 82 randomized subjects. SBP (-20.4+/-15.9 versus -4.7 +/- 12.7 mm Hg, P=0.03) and DBP (-8.7+/-16.3 versus -1.2+/-12.6 mm Hg, P=0.02) showed significant decreases, and high-density lipoprotein-cholesterol (0.1+/-0.6 versus -0.1+/-0.7 mmol l(-1), P=0.04) a significant increase in the magnesium group compared to the placebo group. The adjusted odds ratio between serum magnesium and BP was 2.8 (95%CI: 1.4-6.9). Oral magnesium supplementation with MgCl(2) significantly reduces SBP and DBP in diabetic hypertensive adults with hypomagnesaemia.

Hypomagnesaemia and risk for metabolic glucose disorders: a 10-year follow-up study.

BACKGROUND: Although several lines of evidence suggest that hypomagnesaemia is a risk factor for developing type 2 diabetes, there are no studies regarding the association between hypomagnesaemia and the risk for developing impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Our objective was to examine the association between serum magnesium levels and the risk for developing IFG, IGT and type 2 diabetes. MATERIALS AND METHODS: A total of 1122 individuals (20-65 years of age) were enrolled between 1996 and 1997, and 817 individuals re-examined about 10 years later. New-onset IFG (5.6-7.0 mmol L(-1) fasting glucose), IGT (7.8-11.1 mmol L(-1) glucose 2-h postload), and type 2 diabetes were determined from the number of subjects who had these conditions at the second examination without evidence that they were present at the first one. The relative risk of new-onset metabolic glucose disorders and diabetes (dependent variables) was computed using Poisson regression model adjusted for age, sex, family history of diabetes, waist circumference and homeostasis model assessment for insulin resistance index. Serum magnesium levels of < 0.74 mmol L(-1) (independent variable) defined the exposed group. RESULTS: At baseline, 420 (51.4%) individuals had hypomagnesaemia. New-onset IFG and IGT was identified in 276 (33.8%) individuals. The relative risk for IFG, IGT and IFG + IGT was 1.11 (95% confidence interval, 0.5-5.1), 1.38 (95% confidence interval, 1.1-6.3) and 1.49 (95% confidence interval, 1.1-4.9), respectively. New-onset diabetes was identified in 78 (9.5%) individuals (relative risk 2.54; 95% confidence interval, 1.1-4.1). CONCLUSIONS: Hypomagnesaemia is independently associated with the development of IGT, IFG + IGT and type 2 diabetes, but not with the development of IFG.

Serum magnesium and C-reactive protein levels.

OBJECTIVE: To assess the hypothesis that magnesium deficiency is associated with elevated high-sensitivity C-reactive protein (hsCRP) levels. DESIGN: Community-based cross-sectional study. SETTING: 488 apparently healthy children aged 10-13 years were randomly enrolled from Durango, a city in northern Mexico, through two-stage cluster sampling. MAIN OUTCOME MEASURES: Serum magnesium and hsCRP levels, lipid profile, glucose and insulin levels. RESULTS: A total of 109 (22.3%) and 101 (20.7%) children had elevated hsCRP concentrations and low serum magnesium levels; among them, 87.1% exhibited both. Children who had both elevated hsCRP levels (2.45 (10.6) mg/l) and hypomagnesemia (1.3 (0.3) mg/dl) exhibit the highest fasting glucose (96.0 (13.9) mg/dl), insulin (13.6 (7.5) microU/ml) and triglycerides (131.5 (43.5) mg/dl) levels as well as the lowest HDL-cholesterol (46.4 (9.0) mg/dl) levels. Adjusted multivariate logistic regression analysis showed a strong association between low serum magnesium and high hsCRP levels (odds ratio 4.1; 95% confidence interval 1.3 to 10.8). CONCLUSIONS: Magnesium depletion is independently associated with elevated hsCRP levels, suggesting that hypomagnesemia and low-grade inflammation are interactive risk factors.

Placental immaturity and hyperinsulinaemia in full-term newborns.

BACKGROUND: Evidence from large studies suggests that low birthweight is a risk factor for cardiovascular disease and glucose metabolism disorders in adulthood, but the physiological mechanisms involved in intrauterine growth conditioning low birthweight are not completely understood. The objectives of this study were to determine whether placental immaturity (PI), defined as the lower quartile of placental maturity index (PMI), is associated to hyperinsulinaemia at birth and to identify the risk factors associated with PI. MATERIALS AND METHODS: Cross-sectional study conducted at medical research units of two Mexican general hospitals. A total of 272 full-term newborns with gestational age >/= 38 and < 41 weeks were allocated into the corresponding group according to the quartile distribution of PMI. Data from the lower (PMI < 13.3) and higher quartile (PMI >/= 24.3) were compared. The PMI was estimated by dividing the number of epithelial plates by the average thickness of the epithelial plate. Serum measures included cord glucose and insulin levels of the newborns at birth. RESULTS: A total of 74 (27.2%) children had hyperinsulinaemia at birth, of them 47 (63.5%) with PI. The adjusted multiple regression analysis showed a strong association between PI and hyperinsulinaemia at birth [odds ratio (OR) 2.6; CI 95% 1.3-4.3). Additional adjusted analysis showed that both mother's age

Assessing progression to impaired glucose tolerance and type 2 diabetes mellitus.

BACKGROUND: A prospective evaluation of the relationship between insulin secretion and insulin sensitivity, derived from the fasting state, is needed in clinical practice in order to identify the worsening of glucose metabolism. In this study the authors examine whether the product of insulin sensitivity and insulin secretion, assessed from the fasting state, predicts progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) and from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A cohort of 300 subjects with NGT and 75 subjects with IGT were followed up over a 5-year period. Insulin sensitivity was calculated using the Belfiore index (B) and insulin secretion by the homeostasis model analysis beta-cell (HOMA-beta cell) index: the product of B-beta is expressed as: (40 x Ins(0) pmol L(-1))/Glu(0) mmol L(-1){[(Glu(0) mmol L(-1)x Ins(0) pmol L(-1)) + 1] - 3.5[(Glu(0) mmol L(-1) x Ins(0) pmol L(-1)) - 1]}, where Glu(0) is fasting glucose and Ins(0) is fasting insulin. RESULTS: From baseline at the end of the follow-up period, the product B-beta decreased 10.7% and 52.2% in progressors to IGT and T2DM, respectively. The product B-beta predicts the progression from NGT to IGT [relative risk (RR) 2.7, CI(95%) 1.2-9.1] and from IGT to T2DM (RR 5.3, CI(95%) 1.3-8.55). The cut-off point for the product B-beta that better predicts progression from NGT to IGT is 0.25 (sensitivity 88%, specificity 92%) and from IGT to T2DM 0.15 (sensitivity 92%, specificity 95%). CONCLUSIONS: Adaptation of insulin secretion to compensate for decreased insulin sensitivity during transition to IGT and T2DM can be successfully assessed with simple measures derived from the fasting state. The product B-beta predicts the development to IGT and T2DM.

Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial.

AIMS: The purpose of this study was to identify the effect of pentoxifylline on the urinary protein excretion profile in type 2 diabetic patients. METHODS: 40 type 2 nonhypertensive diabetic patients were randomly allocated to receive either pentoxifylline 400 mg t.i.d. or placebo daily for 16 weeks. Eligible subjects were those with urinary albumin excretion between 20 and 200 microg/min. Subjects receiving angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium antagonists, and diuretics as well as those with reduced renal function, pregnancy, urinary tract infection, and smoking were not included. A 6-month pretreatment stabilization phase aimed to reduce and stabilize fasting serum glucose levels was carried out. Urinary proteins were identified by electrophoresis, and immunodetection was identified by Western blot. Electrophoretic analysis was performed using molecular weight markers of 150, 132, 77, and 66 kDa to identify high-weight proteins, and 54, 41, 36, 27, 21, 14.3, and 12 kDa to identify low-weight proteins. RESULTS: At baseline, subjects in both groups who showed a glomerular tubular pattern did not differ in their urinary excretion profile. The urinary proteins identified were immunoglobulin G, ceruloplasmin, transferrin, and albumin (glomerular pattern) as well as alpha1-antitrypsin, alpha1-acid glycoprotein, collagenase inhibitor, alpha1-microglobulin, trypsin inhibitor, lysozyme, and beta2-microglobulin (tubular pattern). Subjects who received pentoxifylline had reduced urinary excretion of high- and low-molecular weight proteins. CONCLUSIONS: Urinary protein excretion in type 2 diabetic subjects shows a mixed, glomerular and tubular, pattern. Pentoxifylline reduces the excretion of both high and low molecular-weight urinary proteins.

Early decrease of the percent of HOMA beta-cell function is independently related to family history of diabetes in healthy young nonobese individuals.

OBJECTIVE: To determine the relationship between family history of diabetes (FHD) and decrease in percent of HOMA beta-cell function (HOMA-beta%) index in healthy betanon-obese Mexican subjects. MATERIALS AND METHODS: Forty-eight individuals (30 women and 18 men) with FHD were compared vs 48 control subjects (30 women and 18 men) in a cross-sectional study matched by age, sex, and Waist-to-Hip ratio. Pregnancy, obesity, being overweight, alcohol consumption, high blood pressure, and heavy physical activity were exclusion criteria. All the participants were required to have a Body Mass Index < 25 kg/m2 and serum fasting and 2-hours postload glucose levels lower than 6.1 mmol/l and 7.8 mmol/l, respectively. The reciprocal of serum fasting insulin concentrations (1/Ins0) (microU/ml) and HOMA-B% index were used as indicators of insulin sensitivity and beta-cell function. RESULTS: Average age was of 19.4 +/- 3.6 vs 19.8 +/- 2.6, P = 0.66 for the subjects with and without FHD. HOMA-beta% index was significantly lower in the subjects with FHD (186.1 +/- 74.1 vs 252.7 +/- 149.5, P = 0.01). For similar levels of insulin sensitivity, subjects with FHD showed lower HOMA-beta% index than control subjects (P < 0.001). Multivariate regression analysis showed a strong and independent relationship between FHD and decrease of HOMA-beta% index (OR 2.6, CI95% 1.2-4.3, P = 0.01). CONCLUSIONS: This study shows that normal-weight offspring of type 2 diabetes subjects exhibited a significant decrease of HOMA-beta% index suggesting that FHD exerts an independent early negative effect on beta-cell function.

Pentoxifylline is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients--a randomized, equivalent trial.

AIMS: To compare the efficacy of pentoxifylline and captopril on urinary albumin excretion (UAE) rate in non-hypertensive diabetic patients with microalbuminuria. METHODS: 450 subjects were screened; of these 130 eligible, non-hypertensive, type 2 diabetic subjects were enrolled and randomly allocated to receive either pentoxifylline 400 mg t.i.d. (n = 65) or captopril 25 mg t.i.d. (n = 65) for six months in a randomized equivalent trial design study. Patients were eligible to participate if they had microalbuminuria, defined by UAE rate of 20-200 microg/min, and systolic/diastolic blood pressure lower than 140/85 mmHg. Diagnosis of high blood pressure and renal failure were exclusion criteria. In addition, subjects receiving ACE inhibitors or pentoxifylline were not included. RESULTS: Both treatments were well tolerated, without serious adverse events; nonetheless, one subject (1.6%) in the group with pentoxifylline had severe headache, and three (4.7%) subjects in the group with captopril had intense dry cough and nasal congestion that required stopping pentoxifylline and captopril. In addition, slight headache and mild dry cough that did not require specific treatment or interruption of medication were present in two (3.2%) and five (7.8%) subjects treated with pentoxifylline and captopril. Four subjects dropped-out (one in the pentoxifylline group and three in the captopril group). Blood pressure and fasting glucose levels were similar between the two groups throughout the study. The UAE rate decreased from the first month of treatment in the subjects of both groups, a reduction that was sustained in the following months. At the end of the study, the average UAE rate in the subjects of both groups was lower than 25 microg/min. CONCLUSIONS: Pentoxifylline showed to be an effective alternative to ACE inhibitors in reducing UAE in non-hypertensive diabetic patients with microalbuminuria.

Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial.

OBJECTIVE: Although hypomagnesemia reduces insulin sensitivity, benefits of magnesium supplementation to non-diabetic insulin resistant subjects has not been established. Our purpose was to determine whether oral magnesium supplementation with magnesium chloride (MgCl2) 2.5 g daily modify insulin sensitivity in non-diabetic subjects. MATERIAL AND METHODS: This study was a 3 months randomized double-blind placebo-controlled trial. Apparently healthy subjects were eligible to participate if they had insulin resistance (HOMA-IR index equal or greater than 3.0) and hypomagnesemia (Serum magnesium levels equal or lower than 0.74 mmol/l). Subjects were randomized to receive either, MgCl2 2.5 g daily or placebo by 3-months. RESULTS: At baseline there were not significant anthropometric or laboratory differences between both groups. At ending of the study, magnesium-supplemented subjects significantly increased their serum magnesium levels (0.61 +/- 0.08 to 0.81 +/- 0.08 mmol/l, p<0.0001) and reduced HOMA-IR index (4.6 +/- 2.8 to 2.6 +/- 1.1, p<0.0001), whereas control subjects did not (0.62 +/- 0.08 to 0.61 +/- 0.08 mmol/l, p=0.063 and 5.2 +/- 1.9 to 5.3 +/- 2.9, p=0.087). CONCLUSIONS: Oral magnesium supplementation improves insulin sensitivity in hypomagnesemic non-diabetic subjects. Clinical implications of this finding have to be established.

Elevated concentrations of C-reactive protein in subjects with type 2 diabetes mellitus are moderately influenced by glycemic control.

The aim of this study was to establish whether glycemic control results in decrease of C-reactive protein (CRP) in Type 2 diabetic subjects. Newly diagnosed Type 2 diabetic subjects were recruited and followed-up by 6-month intensive medical management. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response, which was an exclusion criterium. CRP was measured by automated microparticle enzyme immunoassay (IMx, Abbott Laboratories, USA). Two-hundred and forty-eight patients were included in the analysis of data. At baseline, average CRP levels were of 9.6 +/- 6.2 mg/l. Only 14 (5.7%) patients showed a fasting glucose equal or lower than 6.1 mmo/l (5.6 +/- 0.4 mmo/l); of them, 6 (42.8%) had elevated CRP levels (8.8 +/- 6.7 mg/l). The fasting glucose in the 234 (94.3%) non-controlled subjects was 13.1 +/- 4.8 mmol/l; of them 179 (76.5%) subjects showed elevated CRP levels (10.9 +/- 6.5 mg/I). At the end of the 6-month follow-up, the average fasting glucose and HbA1c in the overall group decreased from 12.5 +/- 5.0 to 9.0 +/- 1.6 mmol/l, p < 0.00001, and 13.0 +/- 4.9 to 8.9 +/- 2.9%, p < 0.00001, which resulted in a significant reduction of CRP levels (9.6 +/- 6.2 to 6.3 +/- 3.0 mg/l, p < 0.00001). Seventy-one (28.6%) patients reached glycemic control; however, only 29 (40.8%) of them reduced the CRP levels to 3 mg/l or less (1.3 +/- 1.9 mg/l), and the remaining 42 controlled patients maintained high CRP concentration (4.2 +/- 1.2 mg/I), p < 0.00001. Concentration of CRP is moderately influenced by glycemic control in the Type 2 diabetic subjects.