Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma

Background

Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD).

Objectives

We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma.

Methods

High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm.

Results

Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01).

Conclusions

In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies.     

Effect of moderate weight loss on hepatic,pancreatic and visceral lipids in obese subjects

Objective:

To compare the effects of weight loss on visceral and subcutaneous abdominal fat, liver and pancreas lipid content and to test the effects of these changes on metabolic improvement observed after weight loss.

Design:

Weight-loss program designed to achieve a loss of 7–10% of the initial weight.

Subjects:

24 obese subjects (13 males and 11 females) with age ranging from 26 to 69 years and body mass index (BMI) 30.2–50.5 kg m⁻². Measurements: weight, BMI, waist circumference, body composition as assessed by dual-energy X-ray absorptiometry, metabolic variables, leptin, adiponectin, visceral and subcutaneous abdominal fat, liver and pancreas lipid content as assessed by magnetic resonance were evaluated before and after weight loss achieved by hypocaloric diet.

Results:

After a mean body weight decrease of 8.9%, BMI, waist circumference, fat mass, all metabolic variables, homeostasis model assessment of insulin resistance (HOMA), alanine amino transferase, gamma glutamyl transpeptidase, high-sensitivity C-reactive protein (hs-CRP) and leptin, but not adiponectin and high-density lipoprotein-cholesterol, significantly decreased (all P<0.01). Visceral and subcutaneos abdominal fat, liver and pancreas lipid content significantly decreased (all P<0.01). Percent changes in liver lipid content were greater (84.1±3%) than those in lipid pancreas content (42.3±29%) and visceral abdominal fat (31.9±15.6%). After weight loss, percentage of subjects with liver steatosis decreased from 75 to 12.5%. Insulin resistance improvement was predicted by changes in liver lipid content independently of changes in visceral fat, pancreas lipid content, systemic inflammation, leptin and gender.

Conclusion:

Moderate weight loss determines significant decline in visceral abdominal fat, lipid content in liver and pancreas. Reduction of liver lipid content was greater than that of pancreas lipid content and visceral fat loss. Liver lipid content is the strongest predictor of insulin resistance improvement after weight loss.     

Correlation of serum testosterone with insulin resistance in elderly male type 2 diabetes mellitus patients with osteoporosis

Aims/Introduction

The present study was designed to investigate the correlations between the serum testosterone level and insulin sensitivity in elderly male type 2 diabetes patients with osteoporosis.

Materials and Methods

A total of 35 elderly male patients with type 2 diabetes (type 2 diabetes group), 30 elderly male type 2 diabetes patients combined with osteoporosis (DO group) and 30 healthy elderly men (normal control group) participated in the present study. The fasting plasma glucose, fasting insulin, testosterone (T) and estradiol (E₂) were measured. The insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR) and E₂/T were calculated. Then, the correlations of serum testosterone level with ISI and HOMA-IR were analyzed by statistical methods.

Results

The HOMA-IR, E₂ and E₂/T of the type 2 diabetes group and DO group were significantly increased, whereas the bone mineral density, ISI, T and sex hormone binding globulin were decreased compared with those of the normal control group. Serum testosterone levels of the type 2 diabetes group and DO group were negatively correlated to the HOMA-IR (r = −0.496, −0.506; P < 0.05), whereas they were positively correlated to the fasting insulin (r = 0.281, 0.292; P < 0.05) and ISI (r = 0.364, 0.403; P < 0.05).

Conclusions

The reduced level of serum testosterone in elderly male type 2 diabetes patients with osteoporosis might promote insulin resistance.     

Age and outcomes of primary percutaneous intervention for ST elevation myocardial infarction in a tertiary center—are we there yet?

Background Primary percutaneous intervention (PPCI) is the treatment of choice for ST elevation myocardial infarction (STEMI) but robust evidence in the very elderly is lacking. We compared PPCI outcomes between different age quartiles (quartile 1 < 60 years, quartile 2 ≥ 60 to < 70 years, quartile 3 ≥ 70 to < 80 years, quartile 4 ≥ 80 years). Methods Retrospective observational analysis of our Morriston Tertiary Cardiac Centre (Abertawe Bro Morgannwg University Health Board) patients from 2005 to 2010 with STEMI who underwent PPCI. Results Of 434 patients, 57 (13%) were in quartile 4 (≥ 80 years). In older age quartiles, patients were less likely to receive a drug eluting stent (DES, P = 0.001) or glycoprotein IIb/IIIa inhibitor (GPI, P < 0.0001). Increase in age was associated with reduced time to survival (β-coefficient: -0.192, t: -3.70, 95%CI: -4.91 to -1.50, P < 0.0001) as was the presence of cardiogenic shock (β-coefficient: -0.194, t = 3.77, 95%CI: -5.26 to -1.65, P < 0.0001). Use of GPI was associated with increased time to survival (β-coefficient: 0.138, t = 2.82, 95%CI: 1.58–8.58, P = 0.005) but older age quartiles were less likely to receive GPI (P < 0.0001). In-hospital mortality (1.8% quartile 1, 3.6% quartile 2, 10.9% quartile 3 and 12.3% quartile 4, P = 0.002) and 1-year mortality (5.4% quartile 1, 5.5% quartile 2, 16.8% quartile 3 and 24.6% quartile 4, P < 0.0001, respectively) was significantly higher in older age quartiles. Conclusions Increased short term and intermediate term mortality is seen in the very elderly after PPCI. Age and cardiogenic shock were prognostic factors. Intervention should not be based on age alone and awareness regarding prognostic factors can help improve management.     

Extent of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6–6.4%

Aims/Introduction

Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6–6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation.

Materials and Methods

The study participants were 482 men with an estimated visceral fat area of ≥100 cm², HbA1c of 5.6–6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual plasma glucose <200 mg/dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/dL, or casual plasma glucose ≥200 mg/dL.

Results

The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group (P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group.

Conclusions

Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4–5% weight loss in those with HbA1c of 5.6–6.4%.     

Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy

Introduction

The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic).

Methods

Ten subjects with long-standing T1DM (n = 7) or T3cDM (n = 3) on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design.

Results

Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 (p < .05) and from 46 ± 7.7 to 37 ± 6.6 U on day 3 (p < .05) of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 (p < .01) and 34% ± 14% on day 3 (p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; the reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency (p < .002).

Conclusions

A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.     

High sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic syndrome and insulin resistance (CURES-105)

Aim

The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR).

Methodology

From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5.

Results

Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR.

Conclusion

In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.     

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non‐alcoholic fatty liver disease

Aims/Introduction

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease.

Materials and Methods

Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method.

Results

The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = −0.45, P < 0.001; grade r = −0.54, P < 0.001; stage r = −0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = −0.22, P < 0.05) and grade (coefficient = −0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = −0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = −0.62, P = 0.059).

Conclusions

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.     

Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index

Background:

In the Multiethnic Cohort Study, Japanese Americans (JA) have lower mean body mass index (BMI) compared with Caucasians, but show a higher waist-to-hip ratio at similar BMI values and a greater risk of diabetes and obesity-associated cancers.

Objective:

We investigated the abdominal, visceral and hepatic fat distribution in these Asian and Caucasian Americans.

Design:

A cross-sectional sample of 60 female cohort participants (30 JA and 30 Caucasians), of ages 60–65 years and BMIs 18.5–40 kg m⁻², underwent anthropometric measurements and a whole-body dual energy X-ray absorptiometry (DXA) scan: a subset of 48 women also had abdominal magnetic resonance imaging (MRI).

Results:

By design, JA women had similar BMIs (mean 26.5 kg m⁻²) to Caucasian women (27.1 kg m⁻²). JA women were found to have a significantly smaller hip circumference (96.9 vs 103.6 cm; P=0.007) but not a significantly lower DXA total fat mass (25.5 vs 28.8 kg; P=0.16). After adjusting for age and DXA total fat mass, JA women had a greater waist-to-hip ratio (0.97 vs 0.89; P<0.0001), DXA trunk fat (15.4 vs 13.9 kg; P=0.0004) and MRI % abdominal visceral fat (23.9 vs 18.5% P=0.01) and a lower DXA leg fat mass (8.2 vs 10.0 kg; P=<.0001). Their MRI % subcutaneous fat (33.4 vs 30.2% P=0.21) and % liver fat (5.8 vs 3.8% P=0.06) did not significantly differ from that of Caucasian women.

Conclusions:

Our findings build on limited past evidence, suggesting that Asian women carry greater abdominal and visceral fat when compared with Caucasian women with similar overall adiposity. This may contribute to their elevated metabolic risk for obesity-related diseases.     

Reliability of Lightguide Spectrophotometry (O2C?) for the Investigation of Skin Tissue Microvascular Blood Flow and Tissue Oxygen Supply in Diabetic and Nondiabetic Subjects

Background and Aims

Skin microvascular assessment has progressed to an important evaluation in patients with diabetes mellitus. This study was done to evaluate a new device using micro-lightguide spectrophotometry in the assessment of skin microvascular function.

Material and Methods

Twenty nondiabetic subjects (age 46.6 ± 14.8 years; mean ± SD) and 20 diabetic patients (age 59.4 ± 8.4 years) participated in repeated microvascular measurements using micro-lightguide spectrophotometry. This technique allows simultaneous, noninvasive measurement of microvascular blood flow and hemoglobin oxygenation (SO₂) at the same anatomical area in different tissue layers. A skin probe was placed on nonhairy skin at the thenar eminence of the left hand for the measurement of SO₂, and the postischemic reactive hyperemia response (PRH) was measured in skin and underlying muscle tissue.

Results

Repeated measurements in PRH revealed a good correlation at the superficial skin layer (r = 0.97, p < 0.0001) with a coefficient of variation at 9.2 ± 1.7% and at the superficial muscle layer (r = 0.80, p < 0.0002) with a coefficient of variation at 9.7 ± 1.5%. A slightly weaker correlation was observed for the SO₂ measurement at the skin layer (r = 0.69 ± p < 0.0001) with a coefficient of variation at 17.5 ± 3.8% and at the muscle layer (r = 0.48; p = 0.0016) with a coefficient of variation at 18.1 ± 10.5%.

Conclusions

Lightguide spectrophotometry is an easy, noninvasive, and reliable method for simultaneous measurement of superficial microvascular blood flow by laser Doppler fluxmetry and skin oxygenation by spectrophotometry. Further studies are required to clarify the validity of these measures in special patient populations such as diabetes mellitus with specified microvascular complications.     

Plasma homocysteine levels are independently associated with alterations of large artery stiffness in men but not in women

Objectives To investigate the associations of the plasma homocysteine (HCY) levels with the alterations in arterial stiffness in a community-based cohort. The gender differences in these associations were examined. Methods We evaluated the relationship between plasma HCY levels to three measures of vascular function [carotid-femoral pulse wave velocity (CF-PWV), carotid-ankle PWV (CA-PWV) and heart rate corrected augmentation index (AI)] in 1680 participants (mean age: 61.5 years; 709 men, 971 women) from communities of Beijing, China. Results In univariate analysis, plasma HCY levels was positively related to the CF-PWV (r = 0.211, P < 0.0001) and CA-PWV (r = 0.148, P < 0.0001), whereas inversely associated with AI (r = ?0.052, P = 0.016). In multiple linear regression models adjusting for covariants, plasma HCY remained positively related to the CF-PWV (standardized β = 0.065, P = 0.007) in total cases. When the groups of men and women were examined separately, plasma HCY remained positively associated with the CF-PWV (standardized β = 0.082, P = 0.023) in men, whereas the relations between HCY and any of the arterial stiffness indices were not further present in women. Conclusions In Chinese population, plasma HCY levels are independently associated with alterations of large artery stiffness in men but not in women.     

FlexPen? and KwikPen? Prefilled Insulin Devices: A Laboratory Evaluation of Ergonomic and Injection Force Characteristics

Background

Advances in insulin pen technology continue to improve the usability of these devices for patients with diabetes. In this study, ergonomic features and injection force, as measured by glide force (GF) and glide force variability (GFV), were evaluated for the new Humalog^® Mix75/25 KwikPen™ (KwikPen) and compared with the NovoLog^® Mix 70/30 FlexPen^® (FlexPen).

Methods

Fifty prefilled insulin pen devices (25 of each type) were measured for diameter at the cartridge holder and dose window, length and weight with cap attached, and thumb reach at 30 and 60 units. GF was also determined for 100 devices (50 of each type); GFV at 30 and 60 unit doses was calculated for the plateau portion of the force curve based on the minimum and maximum force measured in that portion of the curve.

Results

While FlexPen was lighter in weight than KwikPen, and presented a slightly smaller diameter at the cartridge holder and dose window, KwikPen had a shorter overall pen length compared to FlexPen, with a shorter thumb reach at both the 30- and 60-unit dose settings. The maximum GF for KwikPen was less than FlexPen at both the 30-unit (3.42 vs 5.36 lb, p <0.0001) and 60-unit doses (3.61 vs 5.62, p <0.0001). KwikPen GFV was lower across both doses (mean difference: −0.46 lb at 30 units, −0.44 lb at 60 units; p <0.0001 for both).

Conclusions

While FlexPen was lighter with a slightly smaller cartridge holder and dose window diameter, KwikPen was shorter in length with less thumb reach than FlexPen. KwikPen also demonstrated lower GF and GFV, resulting in a smoother injection profile than FlexPen. These features of KwikPen''s design and function may offer important advantages for the user during insulin administration.     

A Comparative Study of Epicardial Fat Thickness and its Association with Abdominal Visceral Fat Thickness in Obese and Nonobese Type 2 Diabetes Subjects

Context:

The concept of visceral fat and its role in various metabolic disorders is well-known. Epicardial fat (EF) is also visceral fat, and very few studies are done, especially in the Indian subcontinent.

Aims:

To study and establish the relationship of EF thickness (EFT) and abdominal visceral fat thickness (VAT) in obese and nonobese type 2 diabetics and to evaluate the usefulness of EFT as a marker of visceral adiposity.

Settings and Designs:

This cross-sectional study was carried out in the Department of Medicine, JSS Hospital, Mysore, India, between October 2012 and October 2014.

Materials and Methods:

A total of 68 patients were studied. Patients underwent transthoracic echocardiography and ultrasound abdomen. EFT and VAT were measured.

Statistical Analysis:

SPSS version 17.0 (SPSS Inc., Chicago, IL, USA) was used. T-test used for comparing quantitative variables. Correlation analysis was done using Pearson correlation test. P ≤ 0.05 was considered statistically significant. Kruskal-Wallis and Mann-Whitney test were used for analysis.

Results:

The mean value of EFT was 5.92 mm, 7.43 mm, 12.97 mm, 11.27 mm, and 13.8 mm for nonobese, obesity Grade I, II, III, and morbid, respectively (P < 0.0001). The mean EFT between nonobese and obese diabetics was 5.92 mm and 10.2 mm, respectively (P < 0.0001). The mean VAT between nonobese and obese diabetics was 16.58 mm and 38.53 mm, respectively. EFT was significantly correlating with VAT in obese diabetics.

Conclusion:

EFT and VAT were significantly correlated among obese diabetics while not significantly correlated among nonobese diabetics, suggesting obesity is an independent risk factor for visceral adipose tissue deposition both in abdomen as well as in epicardial surface.     

Assessing Quality of Life for New Diabetes Treatments and Technologies: A Simple Patient-Centered Score

Background

A simple quality of life measure is needed for use in diabetes, particularly for the assessment of new treatments and technologies. We devised and validated a patient-centered quality of life (PCQoL) measure that should be applicable to routine clinical practice or trial of therapies.

Methods

People with diabetes completed a two-part, PCQoL questionnaire where they nominated five aspects of general- and diabetes-related life judged most important for their overall quality of life and rated each for current level of satisfaction. Scores derived from the questionnaire were compared with a reference measure—the Diabetes Control and Complications Trial diabetes quality of life (DQoL) score. Both were repeated after 1 month. The participants were 72 diabetic patients (60% with type 1 diabetes); 29 people with type 1 diabetes were treated by continuous subcutaneous insulin infusion (CSII) and 14 were treated by multiple daily insulin injections (MDI).

Results

Patients most often cited family and relationships or fear of complications and hypoglycemia as important facets of quality of life for them. The PCQoL measure was highly correlated with the reference DQoL measure (r = 0.73, p < 0.0001), had high repeatability (r = 91, p < 0.0001), and could be completed in less than 5 minutes. The test was sensitive enough to detect a better quality of life in CSII-treated patients vs MDI-treated patients.

Conclusion

The PCQoL measure is simple, quick, valid, and suitable for routine use in diabetes or trials of new treatments.     

Serum Total Adiponectin Is Associated with Impaired Glucose Tolerance in Asian Indian Females but Not in Males

Objective

Adiponectin may play a role in the development of type 2 diabetes and cardiovascular disease (CVD). However, little is known about the relationship between adiponectin and impaired glucose tolerance (IGT). We investigated the association between adiponectin and IGT and between adiponectin and cardiovascular risk factors among subjects with IGT.

Research Design and Methods

Subjects with normal glucose tolerance (NGT)(n = 571) and impaired glucose tolerance (n = 167) were recruited from the Chennai Urban Rural Epidemiology Study in south India. Serum total adiponectin levels were measured using a radioimmunoassay (Linco Research, St. Charles, MO). High sensitivity C-reactive protein (hsCRP) was estimated by nephelometry.

Results

In sex-stratified analyses, adiponectin was significantly associated with IGT in females [odds ratio (OR): 0.93, 95% confidence interval (CI): 0.872–0.991, p = 0.026] after controlling for age, waist circumference, blood pressure, alcohol consumption, smoking, lipid profile, and glycemic indices; in males there was no significant association (OR = 0.90, 95% CI: 0.798–1.012, p = 0.078). In prediabetic females, adiponectin was not associated with any CVD risk factors (age, waist circumference, blood pressure, cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, fasting glucose, fasting insulin, and insulin resistance level), but was associated negatively with 2-hour postplasma glucose levels (r = –0.243, p < 0.05) and hsCRP (r = –0.219, p < 0.05) after adjusting for demographic and biomedical indices. No associations with CVD risk factors were observed in males with IGT.

Conclusion

Serum total adiponectin levels are associated with IGT, 2-hour postplasma glucose, and hsCRP in Asian Indian females but not in males.     

Low density lipoprotein cholesterol level inversely correlated with coronary flow velocity reserve in patients with Type 2 Diabetes

Objectives To evaluate the association of coronary artery endothelial function and plasma levels of low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in patients with Type 2 Diabetes Mellitus (DM). Methods We investigated 90 participants from our institution between October 2007 to March 2010: non-DM (n = 60) and DM (n = 30). As an indicator of coronary endothelial dysfunction, we used non-invasive Doppler echocardiography to quantify coronary flow velocity reserve (CFVR) in the distal part of the left descending artery after rest and after intravenous adenosine administration. Results Plasma level of LDL-C was significantly higher in patients with DM than in non-DM (3.21±0.64 vs. 2.86±0.72 mmo/L, P < 0.05), but HDL-C level did not differ between the groups (1.01 ± 0.17 vs. 1.05 ± 0.19 mmo/L). Furthermore, the CFVR value was lower in DM patients than non-diabetics (2.45 ± 0.62 vs. 2.98 ± 0.68, P < 0.001). Plasma levels of LDL-C were negatively correlated with CFVR in all subjects (r = -0.35, P < 0.001; 95% confidence interval (CI): -0.52 - -0.15) and in the non-DM (r = -0.29, P < 0.05; 95% CI:-0.51 - -0.05), with an even stronger negative correlation in the DM group (r = -0.42, P < 0.05; 95% CI:-0.68 - -0.06). Age (β = 0.019, s = 0.007, sβ = -0435, 95% CI: -0.033 - -0.055, P = 0.008), LDL-C (β = -0.217, s = 0.105,sβ= -0.282, 95% CI: -0.428 - -0.005, P = 0.045) remained independently correlated with CFVR in the DM group. However, we found no correlation between HDL-C level and CFVR in any group. Conclusions Diabetes may contribute to coronary artery disease (CAD) by inducing dysfunction of the coronary artery endothelium. Increased LDL-C level may adversely impair coronary endothelial function in DM. HDL-C may lose its endothelial-protective effects, in part as a result of pathological conditions, especially under abnormal glucose metabolism.     

Does Visceral Fat Estimated by Dual-Energy X-ray Absorptiometry Independently Predict Cardiometabolic Risks in Adults?

Background:

Abdominal visceral fat, typically measured by computer tomography (CT) or magnetic resonance imaging (MRI), has been shown to correlate with cardiometabolic risks. The purpose of this study was to examine whether a newly developed and validated visceral fat measurement from dual-energy X-ray absorptiometry (DXA) provides added predictive value to the cross-sectional differences of cardiometabolic parameters beyond the traditional anthropometric and DXA adiposity parameters.

Method:

A heterogeneous cohort of 194 adults (81 males and 113 females) with a BMI of 19 to 54 kg/m² participated in this cross-sectional study. Body composition was measured with a DXA densitometer. Visceral fat was then computed with a proprietary algorithm. Insulin sensitivity index (SI, measured by intravenous glucose tolerance test), blood pressures, and lipid profiles, and peak oxygen uptake were also measured as cardiometabolic risk parameters.

Results:

DXA-estimated visceral fat mass was associated with HDL cholesterol (regression coefficient [β] = −5.15, P < .01, adjusted R² = .21), triglyceride (β = 26.01, P < .01, adjusted R² = .14), and peak oxygen uptake (β = −3.15, P < .01, adjusted R² = .57) after adjusting for age, gender, and ethnicity. A subanalysis stratifying gender-specific BMI tertiles showed visceral fat, together with ethnicity, was independently associated with SI in overweight men and moderately obese women (second tertile).

Conclusions:

Without requiring additional CT or MRI-based measurements, visceral fat detected by DXA might offer certain advantages over the traditional DXA adiposity parameters as means of assessing cardiometabolic risks.     

Thawed solvent/detergent-treated plasma: too precious to be wasted after 6 hours?

Background.

Coagulopathy associated with trauma and bleeding requires early administration of haemostatic agents. Solvent/detergent-treated plasma (S/D-plasma) requires thawing and its availability for clinical use is, therefore, delayed. The long-term stability of clotting factors in thawed S/D-plasma has not been thoroughly investigated. The purpose of this study was to evaluate stability of clotting factors and inhibitors in thawed S/D-plasma stored at 4 °C for 6 days.

Materials and methods.

Clotting factor levels and bacterial contamination were investigated using 20 units of S/D-plasma. Fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, von Willebrand antigen (VWF-Ag), plasmin inhibitor, protein C and free protein S were analysed over time.

Results.

After 6 days of storage the results were as follows: fibrinogen 270 mg/dL (−10 mg/dL, p=0.0204), FII 75% (−5%, p<0.0001), FV 88% (−14%, p<0.0001), FVII 81% (−24%, p<0.0001), FVIII 70% (−16%, p<0.0001), FIX 96% (−8, p<0.0001), FX 92% (−1%, p<0.0001), FXI 119% (−4%, p=0.3666), FXII 94% (−2%, p=0.3602), FXIII 89% (−1%, p 0.0019), free protein S 76% (−4%, p<0.0001), protein C 96% (+1%, p=0.0371), antithrombin 92% (−3%, p<0.0001), plasmin inhibitor 29% (−4%, p<0.0299), VWF-Ag 137% (+2%, p=0.2205). FVII and FVIII showed a critical drop of more than 20% or approached the lower quality assurance threshold after storage for more than 24 hours. No S/D-plasma showed bacterial contamination.

Conclusion.

All clotting factors in thawed S/D plasma remained stable for up to 24 hours when stored at 4 °C. Storage of thawed S/D plasma may improve the availability of this product in emergency situations.     

Stearic acid content of abdominal adipose tissues in obese women

Objective:

Subcutaneous (SC) adipose tissue stearic acid (18:0) content and stearoyl-CoA desaturase-1 (SCD1)-mediated production of oleic acid (18:1) have been suggested to be altered in obesity. The objective of our study was to examine abdominal adipose tissue fatty acid content and SCD1 mRNA/protein level in women.

Subjects and methods:

Fatty acid content was determined by capillary gas chromatography in SC and omental (OM) fat tissues from two subgroups of 10 women with either small or large OM adipocytes. Samples from 10 additional women were used to measure SCD1 mRNA and protein expression, total extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 protein as well as insulin receptor (IR) expression levels.

Results:

OM fat 18:0 content was significantly lower in women with large OM adipocytes compared with women who had similar adiposity, but small OM adipocytes (2.37±0.45 vs 2.75±0.30 mg per 100 g adipose tissue, respectively, P⩽0.05). OM fat 18:0 content was negatively related to the visceral adipose tissue area (r=−0.44, P=0.05) and serum triglyceride levels (r=−0.56, P<0.05), while SC fat 18:0 content was negatively correlated with total body fat mass (BFM) (r=−0.48, P<0.05) and fasting insulin concentration (r=−0.73, P<0.005). SC adipose tissue desaturation index (18:1/18:0), SCD1 expression and protein levels were positively correlated with BFM. Moreover, obese women were characterized by a reduced OM/SC ratio of SCD1 mRNA and protein levels. A similar pattern was observed for ERK1/2 and IR expression.

Conclusion:

The presence of large adipocytes and increased adipose mass in a given fat compartment is related to reduced 18:0 content and increased desaturation index in women, independently of dietary fat intake. The depot-specific difference in ERK1/2 expression and activation, as well as in SCD1 and IR expression in obese women is consistent with the hypothesis that they may predominantly develop SC fat, which could in turn help protect from metabolic disorders.     

Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men

Abstract Aims/hypothesis. To compare the relation between intramyocellular lipid content, central obesity and insulin sensitivity in Europeans and South Asians. Methods. Cross-sectional study of 40 South Asian and European non-diabetic men matched for age and body mass index. We measured intramyocellular lipid by proton magnetic resonance spectroscopy of soleus muscle, insulin sensitivity by the short insulin tolerance test, per cent body fat by dual-energy x-ray absorptiometry and visceral fat by single-slice computed tomography of the abdomen. Results. South Asians compared with Europeans had a higher mean per cent body fat (26.8 % vs 22.5 %, p = 0.05) and lower insulin sensitivity (mean ± SEM 2.4 ± 0.2 vs 3.4 %/min ± 0.3, p = 0.013). Mean ( ± SEM) intramyocellular lipid content was higher in South Asians than in Europeans (72.1 ± 7.5 vs 53.6 ± 4.9 mmol/kg dry weight, p = 0.046). In Europeans intramyocellular lipid was correlated with per cent body fat (r = 0.50, p = 0.028), waist:hip ratio (r = 0.74, p < 0.001), visceral fat (r = 0.62, p = 0.004) and insulin sensitivity (r = –0.53, p = 0.016). In South Asians intramyocellular lipid was not significantly related to insulin sensitivity or obesity, and the strongest associations of insulin sensitivity were with fasting plasma triglyceride and waist:hip ratio. Conclusion/interpretation. The association of intramyocellular lipid with insulin sensitivity and obesity in Europeans is consistent with the hypothesis that muscle triglyceride mediates the effect of obesity on insulin sensitivity. The absence of a similar relation of insulin sensitivity to intramyocellular lipid in South Asians suggests that other mechanisms underlie the high insulin resistance observed in this group. [Diabetologia (1999) 42: 932–935] Received: 14 December 1998 and in revised form: 17 March 1999