Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)     

Diabetes Status and Race are Associated With Cardiovascular Risk Markers in Obese Adolescents

ObjectiveThe objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies.MethodsThis was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children’s of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA_1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM).ResultsThere were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA_1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P < .0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA_1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (β, 4.21; P < .0001) and non-HDL-C (β, 4.3; P < .0001).ConclusionObese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA_1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA_1c concentration. (Endocr Pract. 2015;21:165-173)     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

Plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome

ObjetiveTo assess plasma renin and aldosterone levels in obese and non-obese women with polycystic ovary syndrome (PCOS).MethodsObese women (body mass index [BMI] > 30 kg/m2; group A, n = 34) and non-obese women (BMI < 25 kg/m2; group B, n = 13) with PCOS were selected. The control group (group C, n =47) consisted of age-matched women with regular menses and normal ultrasonographic ovaries. Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin, renin, plasma renin activity, and aldosterone levels were measured.ResultsObese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to women in the control group (p < 0.05). Women with PCOS had significantly higher renin levels (group A: 50.2 ± 4.9 picoU/mL, group B: 39.9 ± 2.7 picoU/mL, and group C: 24.6 ± 2.6 picoU/mL), plasma renin activity (group A: 3.7 ± 0.3 ng/mL/h, group B: 3.6 ± 0.3 ng/mL/h, and group C: 2.2 ± 0.4 ng/mL/h), and aldosterone levels (group A: 31.2 ± 3.3 ng/dL, group B: 29.3 ± 2.9 ng/dL, and group C: 22.2 ± 3.9 ng/dL) as compared with controls.ConclusionSignificant differences exist in plasma renin and aldosterone levels between obese and non-obese women as compared with polycystic ovary syndrome and normal controls.     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance

ObjectiveTo determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS).MethodsWe identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation.ResultsThe computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (± 11.8) years and a mean body mass index of 31.4 (± 5.2) kg/m²; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy.ConclusionColesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels. (Endocr Pract. 2007;13:11-16)     

Relationship Between the Environmental Endocrine Disruptor Bisphenol a and Dyslipidemia: A Five-Year Prospective Study

Objective: To investigate whether serum bisphenol A (BPA) concentration is related to the occurrence of dyslipidemia.Methods: A total of 574 adults were enrolled at baseline and followed up for 5 years. Concentrations of serum BPA, triglycerides (TGs), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured. Dyslipidemia was defined as the existence of one or more of the following conditions: high-LDL-cholesterolemia (LDL ≥140 mg/dL), hypertriglyceridemia (TGs ≥150 mg/dL), or low-HDL-cholesterolemia (HDL <40 mg/dL). Participants were stratified into tertiles according to low, median, and high baseline serum BPA levels. Multivariable linear and logistic regression models were used. Data from baseline and follow-up were used for cross-sectional and longitudinal analyses, respectively.Results: In the cross-sectional analysis, compared to subjects in the low BPA tertile, those in the high BPA tertile showed a higher level of LDL cholesterol (108.1 ± 24.4 mg/dL versus 119.5 ± 26.9 mg/dL; P<.05) and a lower level of HDL cholesterol (46.2 ± 11.7 mg/dL versus 39.5 ± 7.5 mg/dL; P<.05). In multivariable linear regression models, Z-transformed BPA was positively associated with LDL cholesterol (β= 0.13, P = .002) and negatively associated with HDL cholesterol (β= -0.28; P<.001). After cross-sectionally adjusting for confounders, subjects in higher BPA exposure was associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, in subjects without low-HDL-cholesterolemia at baseline, each SD increment in baseline BPA was associated with a higher incidence of low-HDL-cholesterolemia after adjustment for confounders (odds ratio [95% confidence interval; CI] 2.76, 95% CI 1.21, 6.29).Conclusion: Cross-sectionally, higher BPA exposure is associated with a higher prevalence of low-HDL-cholesterolemia. Longitudinally, baseline BPA is an independent predictor of the 5-year incidence of low-HDL-cholesterolemia.Abbreviations: BMI = body mass index; BPA = bisphenol A; CI = confidence interval; CVD = cardiovascular disease; EIMDS = environment, inflammation and metabolic diseases study; HDL = high density lipoprotein; LDL = low density lipoprotein; OR = odds ratio; PPAR = peroxisome proliferator-activated receptor; SBP = systolic blood pressure; TG = triglyceride; Z-BPA = Z-transformed bisphenol A     

Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol

ObjectiveTo report our preliminary experience with the revised, more conservative Yale insulin infusion protocol (IIP) that targets blood glucose concentrations of 120 to 160 mg/dL.MethodsWe prospectively tracked clinical responses to the new IIP in our medical intensive care unit (ICU) by recording data on the first 115 consecutive insulin infusions that were initiated. All blood glucose values; insulin doses; nutritional support including intravenous dextrose infusions; caloric values for enteral and parenteral nutrition; and use of vasopressors, corticosteroids, and hemodialysis or continuous venovenous hemodialysis were collected from the hospital record.ResultsThe IIP was used 115 times in 90 patients (mean age, 62 [± 14 years]; 51% male; 35% ethnic minorities; 66.1% with history of diabetes). The mean admission Acute Physiology and Chronic Health Evaluation II score was 24.4 (± 7.5). The median duration of insulin infusion was 59 hours. The mean baseline blood glucose concentration was 306.1 (± 89.8) mg/dL, with the blood glucose target achieved after a median of 7 hours. Once the target was reached, the mean IIP blood glucose concentration was 155.9 (± 22.9) mg/dL (median, 150 mg/dL). The median insulin infusion rate required to reach and maintain the target range was 3.5 units/h. Hypoglycemia was rare, with 0.3% of blood glucose values recorded being less than 70 mg/dL and only 0.02% being less than 40 mg/dL. In all cases, hypoglycemia was rapidly corrected using intravenous dextrose with no evident untoward outcomes.ConclusionsThe updated Yale IIP provides effective and safe targeted blood glucose control in critically ill patients, in compliance with recent national guidelines. It can be easily implemented by hospitals now using the original Yale IIP. (Endocr Pract. 2012;18:363-370)     

Role of proinflammatory markers and NT-proBNP in patients with an implantable cardioverter-defibrillator and an electrical storm

BackgroundSeveral studies have attempted to identify risk factors for the development of an electrical storm (ES), which is defined as ⩾3 separate ventricular tachyarrhythmic (VT/VF) events, but in the majority of studies no triggers have been found. However, little is known about the role of inflammation and NT-proBNP in patients with ES. The aim of this study was therefore to assess the relationship of Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and NT-proBNP serum concentrations in ICD-patients with or without single spontaneous ventricular tachyarrhythmic events (VT/VF) and in ES.MethodsMarkers were determined in 51 patients without ICD-intervention, in 15 ICD-patients with single VT/VF-episodes during 9-months follow-up and in 20 ICD-patients with ES (blood sampling performed within 60 min after fulfilling ES criteria). VT/VF-episodes were analysed by stored ICD-electrograms.ResultsAll patients had idiopathic dilated cardiomyopathy (n = 23) or coronary artery disease (n = 63). Patients with ES revealed significantly higher mean serum concentrations of all markers (IL-6 15.19 ± 10.34 pg/mL, hs-CRP 20.12 ± 14.4 mg/L, NT-proBNP 4799 ± 4596 pg/mL) compared to baseline values of patients with single VT/VF-events during follow-up (IL-6 8.37 ± 5.8 pg/mL (p = 0.03), hs-CRP 4.7 ± 5.3 mg/dL (p < 0.001), NT-proBNP 1913 ± 2665 pg/mL (p = 0.04)) and compared to baseline values of ICD-patients without device intervention (IL-6 4.62 ± 3.66 pg/mL (p < 0.001), hs-CRP 4.1 ± 3.4 mg/L (p < 0.001), NT-proBNP 1461 ± 2281 pg/mL (p < 0.001)). In 9/20 patients presenting with ES (45%) baseline values were available. All markers were significantly higher during ES compared to event-free determination (IL-6 14.54 ± 10.43 vs. 7.03 ± 2.83 pg/mL (p = 0.04), hs-CRP 19.07 ± 16.07 vs. 6.5 ± 3.9 mg/L (p = 0.02), NT-proBNP 4218 ± 2561 vs. 2099 ± 1279 pg/mL (p = 0.03)).ConclusionsElectrical storm is associated with significantly elevated IL-6, hs-CRP and NT-proBNP serum concentrations in ICD-patients with structural heart disease. Thus, ES may be triggered by proinflammatory activity. Combined intraindividual elevation of determined markers might help to identify patients at risk of impending electrical storm.     

Association of Lower Serum Cholesterol Levels with Higher Risk of Osteoporosis in Type 2 Diabetes

ObjectiveTo determine whether a correlation exists between bone mineral density and circulating lipoprotein levels and whether these variables are independently associated with osteoporosis in patients with type 2 diabetes.MethodsIn a cross-sectional analysis, 159 patients with type 2 diabetes were compared with 70 patients without diabetes selected from an outpatient endocrinology clinic in a tertiary care institute during a 1-year period. Variables were gathered through history, physical examination, and laboratory findings, including blood chemistry studies and dual-energy x-ray absorptiometry.ResultsOf the 229 study patients, 86 (37.6%) had osteoporosis. In the patients with diabetes, the mean ± SD of age, weight, total cholesterol, and low-density lipoprotein (LDL) cholesterol in those with and without osteoporosis was 72.3 ± 10.4 years versus 63.6 ± 11.0 years, 74.2 ± 14.4 kg versus 83.7 ± 15.5 kg, 178.4 ± 33.7 mg/dL versus 194.1 ± 33.9 mg/dL, and 100.0 ± 27.1 mg/dL versus 114.2 ± 30.2 mg/dL, respectively (P < 0.01 for all variables). After adjustment for other variables, multiple logistic regression analysis showed that the presence of diabetes was associated with a lower risk of osteoporosis. Similarly, older age and lower body weight, LDL levels, and serum calcium levels were independently associated with lumbar spine osteoporosis in patients with diabetes, in comparison with older age and lower weight in patients without diabetes. Lower weight and older age were associated with femoral neck and total hip osteoporosis in patients with diabetes, in comparison with only older age in patients without diabetes.ConclusionThe presence of type 2 diabetes is associated with a lower risk of osteoporosis. In patients with type 2 diabetes, a lower LDL level is more likely to be associated with osteoporosis at the lumbar spine. (Endocr Pract. 2007;13:620-628)     

Different roles of zinc plus arachidonic acid on insulin sensitivity between high fructose- and high fat-fed rats

AimsThis study was to determine the effects of zinc plus arachidonic acid (ZA) treatment on the insulin action in the specific ZA target organs using hyperinsulinemic euglycemic clamp method.Main methods18 Sprague–Dawley rats weighing ~ 130 g were divided into 3 groups of 6 rats and treated them with 1) normal rat chow, 2) high fructose (60.0%) diet only, or 3) the same fructose diet plus drinking water containing 10 mg zinc plus 50 mg arachidonic acid (AA)/L. In a separate study, male Wistar rats weighing ~ 250 g were fed normal rat chow (n = 4) or high fat (66.5%) diet with drinking water containing zero (n = 9) or 10 mg AA plus 20 mg zinc /L (n = 9). After 4 week treatment, insulin action was assessed using the hyperinsulinemic eguglycemic clamp technique.Key findingsHigh fructose feeding impaired suppression of hepatic glucose output by insulin compared to controls during the clamp procedure (4.39 vs. 2.35 mg/kg/min; p < 0.05). However, ZA treatment in high fructose-fed rats showed a significant improvement of hepatic insulin sensitivity compared to non-treatment controls (4.39 vs. 2.18 mg/kg/min; p < 0.05). Glucose infusion rates in Wistar rats maintained on a high fat diet (HFD) were significantly lower compared to control rats (22.8 ± 1.3 vs. 31.9 ± 1.4 mg/kg/min; p < 0.05). ZA treatment significantly improved (~ 43%) peripheral tissue insulin sensitivity in HFD fed animals (26.7 ± 1.3 [n = 9] vs. 22.8 ± 1.3 mg/kg/min; p < 0.05).SignificanceThese data demonstrate that ZA treatment is effective in improving glucose utilization in hyperglycemic rats receiving either a high-fructose or a high-fat diet.     

Tasa estimada de disposición de glucosa en pacientes menores de 18 años con diabetes mellitus tipo 1 y sobrepeso-obesidad

ObjectiveTo assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight.MethodsA total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age.ResultsNo significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3 ± 1.3 vs 10.1 ± 0.8 mg kg^-1min^-1; p < 0.01). Insulin dose was higher in overweight and obese children, especially in IU/m²/day (37.7 vs 36.1 vs 29.4 respectively; p < 0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5 mg/dL respectively; p < 0.01). No correlation was found between waist circumference and the different markers of insulin resistance.ConclusionsValues of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m²/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk.     

Involvement of src-kinase activation in ischemic preconditioning induced protection of mouse brain

AimsTo investigate the role of src-kinase in ischemic preconditioning induced reversal of ischemia and reperfusion induced cerebral injury in mice.Main methodsBilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining using both by volume and by weight methods differently. Memory was evaluated using elevated plus maze test. Rota rod test was employed to assess motor incoordination.Key findingsBilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) prevented markedly ischemia–reperfusion-induced cerebral injury measured in terms of infarct size (38.5 ± 1.3% and 38.5 ± 2.9% mean infarct of control animals was reduced to 24.3 ± 1.2% and 23.5 ± 1.8% of the preconditioning groups respectively), loss of memory (72.2 ± 3.6 mean transfer latency time of control animals was reduced to 25.6 ± 5.2 of the preconditioning group respectively) and motor coordination (78.3 ± 17.6 s mean falling down latency time of control animals was increased to a mean value of 180.9 ± 6.5 s of the preconditioning groups respectively). SU6656 (2 mg/kg, ip) and PP1 (0.1 mg/kg, ip), highly selective src-kinase inhibitors, attenuated this neuroprotective effect of ischemic preconditioning.SignificanceTherefore, neuroprotective effect of ischemic preconditioning may be due to src-kinase linked mechanism.     

The preparation and antihyperlipidaemic assay of piperlonguminine in vivo

The natural product piperlonguminine (GBN) which is extracted from Piper longum Linn., has high antihyperlipidaemic activity and low toxicity. However, the content of natural GBN in P. longum (0.20–0.25%) is low, and it is not easy to prepare enough sample of natural GBN for further studies, such as large-scale animal experiments. Therefore, in the present study, we tested and confirmed the antihyperlipidaemic activity of chemically synthesised GBN in rats for the first time. The results of the antihyperlipidaemic assay in vivo showed that synthetic GBN had significant lipid-lowering activities. Synthetic GBN not only inhibited body weight gain (66.3 ± 22.50 g vs. 83.9 ± 19.95 g) but also significantly decreased total cholesterol (TC, 9.67 ± 3.32 mmol/L vs. 22.26 ± 5.84 mmol/L), total glycerol (TG, 1.47 ± 0.08 mmol/L vs. 2.86 ± 0.75 mmol/L), and low-density lipoprotein cholesterol (LDL-C, 3.57 ± 1.15 mmol/L vs. 5.44 ± 1.42 mmol/L) while increasing high-density lipoprotein cholesterol (HDL-C, 1.31 ± 0.56 mmol/L vs. 0.68 ± 0.20 mmol/L) in the serum of rats fed a high-fat diet.     

Characterizing Glucose Changes Antecedent to Hypoglycemic Events in the Intensive Care Unit

ObjectiveTo determine whether patterns of glucose changes before hypoglycemia vary according to the severity of the event.MethodsIn this retrospective analysis, point-ofcare blood glucose (POC-BG) data were obtained from the intensive care units (ICUs) of a convenience sample of hospitals that responded to a survey on inpatient diabetes management quality improvement initiatives. To evaluate POC-BG levels before hypoglycemic events, data from patients who experienced hypoglycemia during their time in the ICU were examined, and their glucose changes were assessed against a comparison group of patients who achieved a glycemic range of 80 to 110 mg/dL without ever experiencing hypoglycemia. Absolute glucose decrease, glucose rate of change, and glucose variability before hypoglycemic events (< 40, 40-49, 50-59, and 60-69 mg/ dL) were calculated.ResultsA total of 128 419 POC-BG measurements from 2942 patients in 89 ICUs were analyzed. Patients who experienced the most severe hypoglycemic episodes had the largest absolute drop in their glucose levels before the event (P < .001). The glucose rate of change before a hypoglycemic event increased with worsening hypoglycemia: mean (± standard deviation) glucose rate of change was-1.69 (± 2.98) mg/dL per min before an episode with glucose values less than 40 mg/dL, -0.56 (± 2.65) mg/dL per min before an episode with glucose values 60 to 69 mg/dL, but only -0.39 (± 0.70) for patients who attained a glucose range of 80 to 110 mg/dL without hypoglycemia (P < .001). Glucose variability before an event progressively increased with worsening biochemical hypoglycemia and was least among patients achieving glucose concentrations in the 80 to 110-mg/dL range without hypoglycemia (P < .001).ConclusionsAntecedent glucose change and variability were greater for patients who experienced hypoglycemia. If monitored, these patterns could potentially alert clinicians and help them take preventive measures. Further examination of how these parameters interact with other predisposing risk factors for hypoglycemia is warranted. (Endocr Pract. 2012;18:317-324)     

Elevated Fructosamine Levelsin Acquired Immunodeficiency Syndrome

ObjectiveTo investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.MethodsWe assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (Pao₂) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.ResultsFasting serum glucose was not significantly different between the men with AIDS (87 ± 4 mg/dL) and the healthy male volunteers (84 ± 6 mg/dL); however, A1C (6.9 ± 0.2%) and serum fructosamine levels (288 ± 15 μmol/L) were significantly higher (P < .01) in the patients with AIDS than in the normal subjects (A1C, 5.6 ± 0.1%; fructosamine, 204 ± 14 μmol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P < .01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin < 12 g/dL) or hypoxia (Pao₂ < 95 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 ± 3 mg/L) and the normal subjects (22 ± 4 mg/L).ConclusionOn the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent. (Endocr Pract. 2008;14:686-690)     

Low serum zinc levels in patients undergoing coronary angiography correlate with immune activation and inflammation

IntroductionLow serum zinc concentrations are associated with adverse outcomes. To explain this phenomenon we aimed to investigate whether low zinc levels are related to immune activation, renal function and coronary artery disease (CAD).MethodsSerum concentrations of zinc and the immune activation markers neopterin and C-reactive protein (CRP) were measured in 2048 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.ResultsZinc concentrations did not differ between patients with CAD (mean ± SD: 13.3 ± 2.4 μmol/L) and controls (13.3 ± 2.2 μmol/L; Welch's t test: p = n.s.) but CAD patients had higher neopterin (8.6 ± 7.4 nmol/L) and CRP (9.7 ± 19.6 mg/L) concentrations compared to controls (neopterin: 7.5 ± 4.8 nmol/L, p = 0.0005; CRP: 5.5 ± 10.0 mg/L, p < 0.0001). There was an inverse correlation between serum zinc concentrations and neopterin (Spearman's rank correlation: r_s = ?0.222) and CRP (r_s = ?0.166; both p < 0.0001) concentrations.ConclusionsOur results indicate increased inflammatory processes in patients with low zinc levels. Further studies should clarify whether inflammation related processes such as renal wasting contribute to zinc deficiency and underlie the adverse health consequences of low serum zinc levels.     

Standardized Glycemic Management and Perioperative Glycemic Outcomes in Patients with Diabetes Mellitus who Undergo Same-Day Surgery

ObjectiveTo assess the safety and effectiveness of a standardized glycemic management protocol in patients with diabetes mellitus who undergo same-day surgery.MethodsThe perioperative glycemic management protocol consisted of preoperative instructions and perioperative order sets for management of subcutaneous and intravenous insulin. Patients with known diabetes admitted to same-day surgery during a 10-month period were observed. Patient demographic information and all capillary blood glucose (CBG) values obtained during the sameday surgery visit were collected. Hyperglycemia, defined as a CBG concentration of 200 mg/dL or greater, prompted notification of the attending anesthesiologist. While use of the perioperative order sets was encouraged, the attending anesthesiologist retained the prerogative to treat according to these order sets or their usual care. Physician compliance with the standardized order sets was determined by chart review in the patients who had a documented blood glucose value of 200 mg/dL or greater.ResultsPatients managed with the standardized order sets had greater reductions in CBG values (percentage change, 35 ± 20.5% vs 18 ± 24%, P < .001) and lower postoperative CBG values (186 ± 53 mg/dL vs 208 ± 63 mg/dL, P < .05) than patients who received usual care. No cases of intraoperative or postoperative hypoglycemia (CBG < 70 mg/dL) were observed in either group.ConclusionsA systematic approach to glycemic management that includes instructions for preoperative adjustments to home diabetic medications and order sets for treatment of perioperative hyperglycemia is safe and can be more effective than usual care for ambulatory surgery patients with diabetes. (Endocr Pract. 2011;17:404-411)     

Cholesterol metabolism differs after statin therapy according to the type of hyperlipemia

AimNon-cholesterol sterols reflect cholesterol metabolism. Statins reduce cholesterol synthesis usually with a rise in cholesterol absorption. Common hyperlipemias have shown different patterns of cholesterol metabolism. We evaluated whether cholesterol absorption and synthesis may differ after statin therapy in primary hyperlipemias.Main methodsWe determined lipid profile, apoprotein B and serum sterols (lathosterol, sitosterol, campesterol by gas chromatography/mass spectrometry) before and after statins in 80 untreated hyperlipemic patients, 40 with polygenic hypercholesterolemia (PH) and 40 with familial combined hyperlipemia (FCH).Key findingsAt baseline in FCH lathosterol was significantly higher while campesterol and sitosterol were significantly lower than in PH. After statins, the reduction in LDL-C did not significantly differ between the two groups; in PH there was a significant decrease of lathosterol from 96.1 to 52.6 102 μmol/mmol cholesterol (p = 0.0001) with no significant modifications in campesterol and sitosterol; on the opposite, in FCH lathosterol decreased from 117 to 43 102 μmol/mmol cholesterol (p = 0.0001) and campesterol and sitosterol significantly increased from 38 to 48 102 μmol/mmol cholesterol (p = 0.0001), and from 75 to 86 102 μmol/mmol cholesterol, (p = 0.022), respectively. After statin therapy only in FCH Δ-LDL-C showed a significant inverse correlation with Δ-sitosterol and with Δ-campesterol.SignificancePrimary hyperlipemias show different patterns of response to statins: in PH LDL reduction appears completely “synthesis inhibition” dependent, while in FCH LDL decrease appears to be synthesis dependent, partially limited by absorption increase. Studying cholesterol metabolism before and after hypolipemic therapy might be useful in identifying the best tailored treatment.