Impact of pioglitazone on bone mineral density and bone marrow fat content.

Pioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants. INTRODUCTION: Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters. METHODS: In this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45 mg/day) or matching placebo for 1 year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity. RESULTS: Results were available for 37 subjects who completed the baseline and 1-year evaluations. At 12 months, BM fat increased with pioglitazone (absolute change, +4.1%, p = 0.03), whereas BM fat content in the placebo group decreased non-significantly (-3.1%, p = 0.08) (p = 0.007 for the pioglitazone-placebo response difference). Total hip BMD declined in the pioglitazone group (-1.4%) and increased by 0.8% in the placebo group (p = 0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = -0.56, p = 0.01) in the pioglitazone group, but not within the placebo group (rho = -0.29, p = 0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects. CONCLUSIONS: Pioglitazone use for 12 months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.

Increased fibrosis and angiogenesis in subcutaneous gluteal adipose tissue in nascent metabolic syndrome.

AIMS: Metabolic syndrome (MetS) is globally a common disorder that predisposes to both diabetes and cardiovascular disease (CVD). There is a paucity of data on fibrosis and angiogenesis in adipose tissue (AT) in patients with nascent MetS uncomplicated by diabetes or CVD. Hence, we assayed various indices of fibrosis and angiogenesis in subcutaneous AT (SAT). METHODS: In both patients with MetS and matched controls, we determined fibrosis and the densities of CD31, VEGF and Angiopoietin (Angio) 2 and 1 by immunohistochemistry in gluteal SAT. RESULTS: The fibrosis score was significantly increased in SAT of Met S. Also, both CD31 and VEGF densities were significantly increased. Surprisingly, Angio-2 was not increased and the ratio of Angio2:1 was decreased. Both indices of fibrosis and angiogenesis correlated with biomediators of inflammation. CONCLUSIONS: In conclusion, we report increased fibrosis and paradoxical increased angiogenesis in gluteal SAT and speculate that the increased angiogenesis is a protective mechanism in mitigating further adipose tissue dysregulation in this depot.

Comparison of visceral fat mass measurement by dual-X-ray absorptiometry and magnetic resonance imaging in a multiethnic cohort: the Dallas Heart Study.

BACKGROUND/OBJECTIVES: Visceral adipose tissue (VAT) mass, a risk factor for cardiometabolic complications of obesity, is usually measured by magnetic resonance imaging (MRI) but this method is not practical in a clinical setting. In contrast, measurement of VAT by dual-x-ray absorptiometry (DXA) appears to circumvent the limitations of MRI. In this study, we compared measurements of VAT mass by MRI and DXA in the large, multiethnic cohort of the Dallas Heart Study (DHS). SUBJECTS/METHODS: About 2689 DHS participants underwent paired measurement of VAT by MRI and DXA. Sex-stratified analyses were performed to evaluate the correlation and agreement between DXA and MRI. Model validation was performed using bootstrapping and inter-reader variability was assessed. RESULTS: Mean age of the cohort was 44 years, with 55% female, 48% Black and 75% overweight/obese participants. Regression analysis showed a linear relationship between DXA and MRI with R(2)=0.82 (95% confidence interval (CI) 0.81-0.84) for females and R(2)=0.86 (95% CI 0.85-0.88) for males. Mean difference between methods was 0.01 kg for females and 0.09 kg for males. Bland-Altman analysis showed that DXA tended to modestly underestimate VAT compared with MRI at lower VAT levels and overestimate it compared with MRI at higher VAT levels. Results were consistent in analyses stratified by race, body mass index status, waist girth and body fat. Inter-individual reader correlation among 50 randomly selected scans was excellent (inter-class correlation coefficient=0.997). CONCLUSIONS: VAT mass quantification by DXA was both accurate and valid among a large, multiethnic cohort within a wide range of body fatness. Further studies including repeat assessments over time will help determine its long-term applicability.

Determinants of change in bone mineral density and fracture risk during bisphosphonate holiday.

UNLABELLED: In a retrospective analysis of 208 osteoporotic patients followed during a bisphosphonate holiday, lower body weight and risedronate use were associated with a more rapid decline in bone mineral density during the bisphosphonate holiday, while bone mineral density (BMD) trends were similar in patients who sustained vs. did not sustain a fracture. INTRODUCTION: A drug holiday has been suggested for some bisphosphonate-treated patients with osteoporosis to minimize potential side effects from prolonged use. However, there is limited information on the evolution of BMD during a bisphosphonate holiday. Our study analyzed the longitudinal course of BMD following bisphosphonate discontinuation and assessed its determinants. METHODS: Retrospective single-center cohort study of osteoporosis patients treated with alendronate or risedronate for at least 2 years and then discontinued their bisphosphonate for a drug holiday. Patients were stratified by bisphosphonate type and by fracture occurrence during drug holiday. RESULTS: A total of 208 patients were included in this analysis (87.5 % female). At the time of bisphosphonate cessation, mean ± SD age was 66.9 ± 8.9 years and BMI 24.5 ± 4.4 kg/m(2). Duration of bisphosphonate treatment was 5.2 ± 2.3 years, and follow-up during holiday was 3.3 ± 1.7 years. During the first 2 years of the holiday, BMD remained stable at the lumbar spine and femoral neck, but declined significantly at the total hip. BMD declined significantly at all sites thereafter. Significant predictors of BMD decline during bisphosphonate holiday included lower BMI at the start of the holiday and change in body weight during the holiday. BMD decline was more pronounced in former risedronate compared to former alendronate users. BMD trends were similar in patients who sustained vs. did not sustain a fracture during the holiday. CONCLUSIONS: BMD at the total hip declines significantly within 1 year of bisphosphonate discontinuation, particularly in lean patients. Additional studies are needed to identify predictors of fracture incidence during a bisphosphonate holiday.

Acute and chronic immune biomarker changes during interferon/ribavirin treatment in HIV/HCV co-infected patients.

Chronic viral infections lead to persistent immune activation, which is alleviated by eradicating or suppressing the infection. To understand the effects of interferon treatment on immune system activation by chronic infections, we evaluated kinetic patterns of a broad spectrum of serum biomarkers during HCV treatment in HIV/HCV co-infected patients. HCV viral load and 50 biomarkers were analysed at baseline and 27 time points during pegylated interferon-alpha and ribavirin (IFN/RBV) treatment of 12 HIV/HCV co-infected patients. We evaluated biomarker changes from baseline for each time point and biomarker correlations with clinical parameters, treatment response and liver histopathology. IL-1α, IL-12p40, IL-1RA, IP-10, MIG, MIP-1α/1ß, HGF, sCD40L, TRAIL and leptin increased in the first day. IL-12p70, IL-17A, IL-10, GROα, IL-8, MCP-3, IL-4 and M-CSF peaked later during week 1. IL-1α, HGF, IP-10, MIP-1α, TRAIL, sCD40L, IL-10, IL-12p70, MCP-3, FGFb, ENA-78, TGF-ß, IL-2, IFN-γ, IL-6, IL-15, IL-7 and PDGF-BB decreased below baseline over the course of treatment. Higher BMI, baseline HCV viral load and leptin levels were associated with lack of sustained virologic response. ENA-78 was associated with sustained viral response. Positive correlations were found between liver inflammation and baseline CD4 count, sVCAM and HGF; fibrosis stage and HGF; liver steatosis, BMI and leptin. Our findings suggest IFN/RBV treatment initially increases levels of several biomarkers, but eventually leads to a decline in many immune markers. These findings shed light on the relationship between IFN treatment and immune activation by chronic viral infections, such as HCV.

Circulating pathogen-associated molecular pattern - binding proteins and High Mobility Group Box protein 1 in nascent metabolic syndrome: implications for cellular Toll-like receptor activity.

OBJECTIVE: The Metabolic Syndrome, (MetS) a global epidemic, is a state of low grade chronic inflammation and confers an increased risk for diabetes and CVD. We have previously reported increased activity of the pathogen recognition receptors, Toll-like receptors (TLRs), TLR2 and TLR4 in MetS. We hypothesized that increased TLR activity in MetS is due in part to increased levels of circulating PAMP-binding proteins, soluble CD14 (sCD14), lipopolysaccharide binding protein (LBP) and the damage associated molecular pattern (DAMP), High Mobility Group Box protein 1 (HMGB-1). METHODS: We measured sCD14, LBP and HMGB-1 in fasting plasma from nascent MetS (n = 37) and healthy control subjects (n = 32) by ELISA. We also investigated the effects of sCD14 and LBP on TLR4 activity in human aortic endothelial cells (HAECs). RESULTS: Following adjustment for body mass index and waist circumference, sCD14, LBP and HMGB-1 levels remained significantly increased in MetS. Also their levels increased with increasing numbers of MetS risk factors. Only sCD14 correlated significantly with monocyte TLR4 protein and activity. None of these soluble biomarkers correlated with TLR2 protein. Both sCD14 and HMGB-1 correlated significantly with HOMA-IR. In LPS primed HAECs, sCD14 compared to LBP, resulted in a greater increase in both TLR4 abundance and inflammatory biomediators (NF-κB, IL-1ß, IL-8 and TNF-α). CONCLUSION: Thus, we make the novel observation that sCD14 reflects increased monocyte TLR4 protein and activity in nascent MetS and by contributing to increased cellular inflammation could explain, in part, the increased risk for diabetes and CVD.

A multicentre, cross-sectional study on quality of life in patients with cutaneous lupus erythematosus.

BACKGROUND: A study at the University of Pennsylvania (UPenn) Medical Center demonstrated that quality of life in patients with cutaneous lupus erythematosus (CLE) is negatively impacted. Whether patients with CLE in other geographic locations have similar quality of life is unknown. OBJECTIVES: We sought to compare quality of life indicators between patients with CLE at the University of Texas Southwestern (UTSW) Medical Center at Dallas and those at UPenn. METHODS: Patients with CLE (total n=248) at UTSW (n=91) and UPenn (n=157) completed the Skindex-29 +3 and Short Form-36 (SF-36) surveys related to quality of life. Additional information, including demographics, presence of systemic lupus erythematosus (SLE) and disease severity, was collected from UTSW patients with CLE. RESULTS: Most Skindex-29 + 3 and SF-36 subdomain scores between UTSW and UPenn patients with CLE were similar. However, UTSW patients with CLE were significantly more affected in the functioning and lupus-specific Skindex-29 + 3 domains, and physical functioning, role-physical and general health SF-36 subscales than UPenn patients with CLE (P<0·05). Factors related to poor quality of life in UTSW patients with CLE include sex, income, education, presence of SLE, and skin disease activity. CONCLUSIONS: Most quality of life indicators were similar between the two CLE populations. Differences in psychosocial behaviour, and a larger proportion of patients with SLE and females in the UTSW group likely attributed to differences in a minority of Skindex-29+3 and SF-36 subdomains. Capturing data from CLE populations in different locations provides a more thorough picture of the quality of life that patients with CLE experience on a daily basis with special attention to quality of life issues in select patients with CLE.

25-Hydroxyvitamin D levels in African-American and Caucasian/Hispanic subjects with cutaneous lupus erythematosus.

BACKGROUND: Because exposure to ultraviolet radiation accounts for a significant portion of endogenous vitamin D production, subjects with cutaneous lupus (CLE) who practise sun-protective measures are at risk for vitamin D insufficiency. Previous studies have shown light-skinned subjects with CLE to have lower serum 25-hydroxy (25-OH) vitamin D levels than normal controls. OBJECTIVES: To assess the status of vitamin D insufficiency in dark-skinned individuals with CLE. METHODS: We performed a cross-sectional study comparing serum 25-OH vitamin D levels in 25 African-American (AA) subjects with CLE and 26 normal AA subjects matched by age, sex and season in Dallas, Texas. A questionnaire on demographics, medical history and lifestyle habits was administered to determine factors potentially affecting vitamin D levels. Findings were contrasted to a similar comparison in 26 Caucasian and Hispanic (C/H) subjects with CLE and 24 normal C/H subjects matched by age, sex and season. RESULTS: We found similar mean±SD 25-OH vitamin D levels in AA subjects with CLE (52·0±18·5nmolL(-1) ) and normal AA subjects (54·8±21·2 nmolL(-1) ) (P=0·62). Almost half of AA subjects in both groups were vitamin D insufficient. A larger difference in 25-OH vitamin D levels was found between C/H subjects with CLE (59·4±21·0nmolL(-1) ) and normal C/H subjects (70·5±27·4nmolL(-1) ) (P=0·12). Two-way anova demonstrated that skin colour (AA vs. C/H) had a significant effect on 25-OH vitamin D levels (P=0·008), although CLE status (CLE vs. normal) did not (P=0·13). CONCLUSIONS: Providers are encouraged to address vitamin D insufficiency concerns in all dark-skinned individuals. Future studies should stratify subjects by skin colour in determining differences between subjects with CLE and normal controls.

A pilot study to investigate the effect of plate size on meal energy intake in normal weight and overweight/obese women.

BACKGROUND: Smaller plates are often recommended as a strategy for controlling energy intake; however, the effect of plate size on meal energy intake in normal weight compared to overweight or obese individuals is not known. The present study aimed to investigate this further. METHODS: Ten normal weight [mean (SD) body mass index, 21.7 (2.0) kg m(-2) ] and 10 overweight or obese [31.7 (3.6) kg m(-2) ] women attended a metabolic laboratory on two separate days for lunch. In this cross-over study, subjects were randomly assigned to eat lunch using either a small (21.6 cm) or a large (27.4 cm) plate. Each subject self-served spaghetti mixed with tomato sauce from an individual serving bowl onto the assigned plate, and ate until satisfied. The meal was consumed alone at a private table. During the second study day, each subject underwent the same procedure but used the alternate size plate. The amount eaten and energy consumed were calculated and a mixed effects analysis of variance model was used to compare energy intakes. RESULTS: Energy intakes using the small and large plate were 1356 (515) and 1365 (393) kJ, respectively, in normal weight subjects and 1314 (632) and 1226 (431) kJ, respectively, in overweight/obese subjects. Neither plate size, nor plate size by weight status significantly affected meal energy intake. There was no plate size by weight status effect on ratings of palatability, hunger, satiety, fullness or prospective consumption. CONCLUSIONS: Plate size did not affect energy intake from a single meal in either the normal weight or overweight/obese subjects.

Decreased number and impaired functionality of endothelial progenitor cells in subjects with metabolic syndrome: implications for increased cardiovascular risk.

OBJECTIVE: Metabolic syndrome (MetS) is characterized by low-grade inflammation and confers an increased risk for cardiovascular disease. Endothelial progenitor cells (EPCs) are a measure of vascular health and are decreased in patients with various risk factors for cardiovascular disease (CVD). There is a paucity of data examining the EPC status especially in terms of their functionality in MetS subjects without diabetes or cardiovascular disease. We aimed to enumerate and functionally characterize EPCs in subjects with MetS in comparison to healthy controls. METHODS: The study was performed at the University of California Davis Medical Center. Healthy controls (n=31) and MetS (n=46) subjects were included in the study. EPCs were enumerated in fasting blood by KDR/CD34 dual positivity. Functionality was assessed by the colony forming units (CFU) assay, migration and tubule formation. RESULTS: Subjects with MetS had significantly decreased number of EPCs compared to control subjects. Furthermore, EPCs from MetS subjects depicted significantly impaired clonogenic capacity, i.e., decreased colony forming units, and impaired capacity to incorporate into tubular structures suggesting functional impairment of EPCs from MetS subjects. CONCLUSIONS: We make the novel observation that MetS subjects without diabetes or CVD have decreased EPC number and impaired functionality as compared to control subjects. These findings could contribute to the increased CV risk in this population.

Comparison of the absorption of calcium carbonate and calcium citrate after Roux-en-Y gastric bypass.

INTRODUCTION: Roux-en-Y gastric bypass (RYGB) restricts food intake. Consequently, patients consume less calcium. In addition, food no longer passes through the duodenum, the main site of calcium absorption. Therefore, calcium absorption is significantly impaired. The goal of this study is to compare two common calcium supplements in gastric bypass patients. METHOD: Nineteen patients were enrolled in a randomized, double-blinded, crossover study comparing the absorption of calcium from calcium carbonate and calcium citrate salts. Serum and urine calcium levels were assessed for peak values (C (max)) and cumulative calcium increment (area under the curve [AUC]). Serum PTH was assessed for minimum values (PTH(min)) and cumulative PTH decrement (AUC). Statistical analysis was performed using a repeated analysis of variance model. RESULTS: Eighteen subjects completed the study. Calcium citrate resulted in a significantly higher serum C (max) (9.4 + 0.4 mg/dl vs. 9.2 + 0.3 mg/dl, p = 0.02) and serum AUC (55 + 2 mg/dl vs. 54 + 2 mg/dl, p = 0.02). Calcium citrate resulted in a significantly lower PTH(min) (24 + 11 pg/ml vs. 30 + 13 pg/ml, p = 0.01) and a higher AUC (-32 + 51 pg/ml vs. -3 + 56 pg/ml, p = 0.04). There was a non-significant trend for higher urinary AUC in the calcium citrate group (76.13 + 36.39 mg/6 h vs. 66.04 + 40.82, p = 0.17). CONCLUSION: Calcium citrate has superior bioavailability than calcium carbonate in RYGB patients.

Relationship of psoriasis severity to obesity using same-gender siblings as controls for obesity.

BACKGROUND: Psoriasis is a multifactorial disease affected by both genetic and environmental factors. Several comorbid conditions, such as smoking, depression and obesity have been found to be associated with psoriasis. This study addressed the association of psoriasis and obesity using same-gender full siblings as controls, correlating between body mass index (BMI) and severity of psoriasis as determined by body surface area (BSA) and the Physician's Global Assessment (PGA). METHODS: In total, 88 patients undergoing outpatient treatment for psoriasis were surveyed for demographic information, psoriasis history, social history, personal and family medical history, whether they had a same-gender full sibling and if so, the age, weight and height of the sibling. Height, weight, PGA scores and percentage of BSA affected by psoriasis, were recorded for each patient. BMI was calculated for each patient and their same-gender full sibling. RESULTS: A positive association between psoriasis severity and BMI was found. PGA score increased with BMI (Spearman's correlation, r(s) = 0.29, P = 0.007). There was also a positive correlation between BMI and BSA%, r(s) = 0.24, P = 0.02. A significant difference in BMI between patients with psoriasis and the same-gender full sibling control was seen for women (mean +/- SD 30.2 +/- 10.2 vs. 27.6 +/- 7.3 kg/m(2), respectively, P = 0.02), but not for men. CONCLUSION: In this study, psoriasis severity was found to be related to the level of obesity. Using same-gender siblings as genetic controls for predisposition to both obesity and psoriasis, patients with psoriasis were more likely to have a higher BMI, particularly for women. This study reinforces the need to treat the whole patient and to encourage healthy living, such as maintaining an appropriate weight, proper eating habits and exercise. Limitations of this study include the relatively small number of patients enrolled, potential inaccuracies in sibling BMIs calculated from information provided by patients, and a lack of information about dietary habits, exercise and lifestyle.

[Inappropriateness of hospital use in two acute geriatrics department: description of the phenomenon and analysis of risk factors]. / Non-pertinence hospitalière dans deux services de gériatrie aiguë: description du phénomène et étude des facteurs de risque.

BACKGROUND: Inappropriateness of hospital use occurs when a gap between the patient's needs and the level of care delivered exists. Taking into account the improvement of number of acute geriatric care, it appears relevant to study the rate and causes of inappropriate hospital use in this context. METHODS: All patients in two services of acute geriatrics were included: medical and socioeconomic data were collected, the appropriateness of each day of their hospitalization was evaluated using the French version of the Appropriateness Evaluation Protocol and the inappropriate days' Causes Analysis Protocol. Risk factors of having at least one inappropriate day occurring during the stay were searched using relevant statistical tests. A logistic regression model assessed influence of independent variables on the risk of inappropriateness. RESULTS: Only the existence of cognitive impairment and the department where the hospitalization takes place were found to be risk factors of inappropriateness. The ranking of inappropriateness according to the causes is the same in the two services, yet with statistically different rates, in particular for causes related to waiting for admission in subacute or long-term care institutional network and for a service provided outside the hospital where the patient was admitted. In the two departments, over 25% of the inappropriate days were related to a patient's or his family's choice. CONCLUSION: Access to subacute or long-term care institution is the first cause of inappropriate hospital use in the two departments. The importance of the rate of inappropriate days related to a choice of the patient or his family was probably a Geriatric specificity. Furthermore, in view of reducing the inappropriate hospital use, attention should be particularly paid on patients with cognitive impairment.

Weight gain in type 2 diabetes mellitus.

OBJECTIVE: To investigate the potential causes of weight gain using insulin and combination therapy in type 2 diabetes. DESIGN AND METHODS: This was an open-label prospective study of 6-month duration. Randomization was performed to insulin monotherapy, insulin and pioglitazone 30 mg daily, or insulin and metformin up to 2000 mg daily. Fifty-seven subjects with poorly controlled type 2 diabetes were enrolled. The goal was to achieve a normal haemoglobin A1c (HbA1c) (<5.6%). Weight, resting energy expenditure (REE), reported energy intake and total energy expenditure, HbA1c, glycosuria, plasma leptin, ghrelin and adiponectin levels, and body fat were measured. RESULTS: A total of 49 subjects completed the study. At baseline, weight was 89.4 +/- 22.9 kg and HbA1c was 11.1 +/- 1.5%. Weight increased by 7.46, 7.60 and 7.12 kg in the monotherapy, metformin and pioglitazone groups, respectively [p = 0.98 between and <0.0001 within the groups by repeated measures-analysis of variance (RM-anova)]. HbA1c dropped to 7.8 +/- 0.9% in the monotherapy arm, 7.6 +/- 1.0% in the metformin arm and 7.2 +/- 1.2% in the pioglitazone arm. Reported energy intake decreased. Glycosuria decreased but was not correlated with weight gain, while HbA1c changes were correlated with weight gain. REE per lean mass decreased (p = 0.04 by RM-anova). The subcutaneous fat areas in the insulin monotherapy and pioglitazone arms showed increases (p = 0.02 and 0.004 respectively). CONCLUSIONS: Weight gain was probably not due to an increase in food intake, while REE per lean body mass decreased, suggesting a role for increased efficiency in fuel usage due to improved glycaemic control. A drop in glycosuria probably also contributed to weight gain. In the monotherapy and pioglitazone arms, the subcutaneous fat areas increased.

The visceral and subcutaneous fat changes in type 1 diabetes: a pilot study.

OBJECTIVE: To evaluate the effects of improved glycaemic control on the abdominal visceral and subcutaneous fat in type 1 diabetes. RESEARCH DESIGN AND METHODS: Sixteen subjects were enrolled for this 6-month study. The goal was to achieve normal haemoglobin A1c (HbA1c <5.6% in our laboratory). T1-weighted magnetic resonance imaging was used to measure the abdominal subcutaneous and visceral fat areas at the L2-L3 disk level. Activity and energy intake were assessed using a weekly recall and food diary respectively. Plasma leptin, ghrelin and adiponectin levels were measured at baseline and at 6 months. RESULTS: Twelve subjects completed the study. HbA1c was 10.4 +/- 2.2% at baseline, and abdominal visceral to subcutaneous fat ratio was 0.29 +/- 0.15. HbA1c dropped to 8.0 +/- 1.4% at 6 months (p = 0.009). There was a +1.85 kg weight change in 6 months (p = 0.30), whereas the visceral to subcutaneous fat ratios changed to 0.36 +/- 0.18 (p = 0.22). Daily metabolic equivalents (METs) of activity at 6 months correlated with a decrease in the visceral to subcutaneous fat ratios (r = -0.80, p = 0.01). Ghrelin level changes correlated negatively with the changes in the visceral to subcutaneous fat ratio (p < 0.01). CONCLUSIONS: The visceral to subcutaneous fat changes had a negative correlation with the physical activity METs at 6 months but not with HbA1c changes in this study. The correlation between the changes in ghrelin and the visceral to subcutaneous fat ratios is intriguing, but a larger study may be needed to confirm this finding.

Potential causes of weight gain in type 1 diabetes mellitus.

AIM: To investigate the potential causes of weight gain with insulin therapy and improved diabetic control in type 1 diabetes mellitus. METHODS: This was an open-label prospective study of insulin therapy of 6 months duration in an academic medical centre. Twenty-one subjects with type 1 diabetes were enrolled. The goal was to achieve an haemoglobin A1c (HbA1c) in the range of individuals without diabetes (<5.6%). At baseline, 3 and 6 months, weight, resting energy expenditure, appetite assessment, food intake, activity level, HbA1c and 24-h glycosuria and urea nitrogen were measured. Plasma leptin, ghrelin and adiponectin levels and body fat were measured at baseline and 6 months. RESULTS: At baseline, average weight was 73.7 +/- 17.4 kg and HbA1c was 10.0 +/- 2.2%. Weight increased by 2.15 kg (2.69% of baseline) by 6 months whereas the HbA1c dropped by 1.71% (16.3%) to 7.9%. Energy intake differences between 3 and 6 months had a negative correlation with weight gain, but the changes in glycosuria, appetite scores and the frequency of hypoglycaemia did not correlate with weight gain. Glycaemic control did not correlate with weight change but tended to correlate with fat mass increase (p = 0.064; r = -0.51). An increase in the activity levels between 3 and 6 months correlated with decreasing fat mass (p = 0.037; r = -0.74). The changes in the appetite scores had a negative correlation with fat mass gain (p = 0.035; r = -0.61). The changes in lean body mass correlated with protein and total energy intake (p = 0.007, r = 0.85 and p = 0.003, r = 0.73 respectively). The changes in leptin levels correlated with weight gain. CONCLUSIONS: The lipogenic effect of insulin with subsequent increase in fat mass may be the primary cause of this weight gain that can be attenuated by the increases in the activity levels. The negative correlation of energy intake and appetite scores with fat mass gain suggests that they do not play a significant role in fat mass gain whereas energy intake did correlate with lean body mass gain.

The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy.

BACKGROUND: Lipodystrophy in HIV-infected (LDHIV) patients receiving protease inhibitors (PIs) is associated with dyslipidaemia. Whether lifestyle factors play a role in dyslipidaemia in LDHIV subjects on PIs is not well characterized. METHODS: A total of 45 LDHIV male and six LDHIV female patients on PIs were recruited, and data were collected on smoking, exercise, diet (by 3-day food record), and fasting levels of serum lipids and lipoproteins. The relationships between lifestyle factors and metabolic variables were analysed in male patients by Spearman's correlation test and the significant relationships were further analysed by adjusting for age, PI duration, and waist circumference by Spearman's partial correlation test. RESULTS: In men, mean (+/-standard deviation) serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C were 212+/-70, 35+/-7.3, 325+/-230 and 169+/-44 mg/dL, respectively. Sixty-seven percent of the men exercised regularly and 31.1% smoked. The reported diet was high in cholesterol (390+/-212 mg) and percentage energy from saturated (12.2+/-3.3%) and trans (2.4+/-1.2%) fats, and low in soluble fibre (6.9+/-2.3 g) compared with recent dietary guidelines. Following adjustments for the confounding variables, percentage energy intake from total protein and animal protein was positively related to TC (r=0.44, P<0.01 and r=0.37, P<0.05, respectively), TG (r=0.40, P<0.01 and r=0.46, P<0.01, respectively) and non-HDL-C (r=0.56, P<0.001 and r=0.49, P<0.01, respectively), that from trans fat was positively related to TG (r=0.34, P<0.05), and soluble fibre was negatively related to non-HDL-C (r=-0.41, P<0.01). Moderate to heavy aerobic exercise tended to be associated with higher HDL-C (r=0.30, P=0.07) whereas smoking was not associated with any of the metabolic variables. CONCLUSIONS: Increased intake of total protein, animal protein and trans fat, and reduced soluble fibre consumption contribute to dyslipidaemia in LDHIV subjects on PIs.