Treatment of obesity by controlled fasting in patients with type 1 diabetes mellitus effect on insulin sensitivity and glucose metabolism

Treatment of obesity by controlled fasting in patients with type 1 diabetes mellitus effect on insulin sensitivity and glucose metabolism

Nutrition 28 (2012) 106–107 Contents lists available at ScienceDirect Nutrition journal homepage: www.nutritionjrnl.com Abstracts Selected Abstrac...

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Nutrition 28 (2012) 106–107

Contents lists available at ScienceDirect

Nutrition journal homepage: www.nutritionjrnl.com

Abstracts

Selected Abstracts of the 23rd Annual Congress of the Czech Society for Clinical Nutrition and Intensive Metabolic Care Hradec Kralove, Czech Republic, February 2011 Edited by Vladimir Palicka, M.D., Ph.D., on behalf of the Czech Society for Clinical Nutrition and Intensive Metabolic Care CHOLESTEROL METABOLISM IN PATIENTS WITH DIABETES MELLITUS TYPE 1 - IMPACT OF WEIGHT REDUCTION (NEW RESULTS)  J. Lesná, F. Musil, A. Tichá, R. Hyspler, V. Bláha, L. Sobotka, A. Smahelová , Charles University in Prague, Faculty of Medicine in Hradec Kr alove , Department of Gerontology University Hospital in Hradec Kr alove and Metabolism, Czech Republic Background and aims: A redundant fat mass represents a risk factor for malfunction of cholesterol metabolism with enhanced endogenous synthesis and decreased absorption of cholesterol. Diabetes mellitus type 1 is on the contrary characterized by the reduced endogenous synthesis and increased absorption of cholesterol. The aim of this study was to characterize cholesterol metabolism in obese patients with type 1 diabetes mellitus and to elucidate the relationship between the reduction of fat tissue, insulin resistance and consequent changes in cholesterol metabolism. Materials and methods: Plasma levels of cholesterol, non-cholesterol sterols (lathosterol-marker of cholesterol synthesis; campesterol, sitosterol – markers of cholesterol absorption) and squalene were estimated in obese type 1 diabetics (n ¼ 14, BMI > 30kg/m2, age 29-62 y). Measurements were repeated after one week of fasting (hospital setting), a month on a diet containing 150g saccharides per day and a year on a diet with 225g saccharides per day. Simultaneously, a control group of non-obese type 1 diabetics (n ¼ 14, BMI < 24, 21-57 y) was investigated. Total cholesterol, high-density lipoproteins, low-density lipoproteins and triacylglycerols were estimated enzymatically. Gas chromatography with a flame ionisation detector was used to estimate squalene and noncholesterol sterols. The data were statistically analyzed by software Sigma Stat – One way ANOVA repeated measurement. Results: During the one-month reduction program obese diabetics lost on average 7 kg of their body weight, after a year on a standard diabetic diet patients gained 3kg of the body weight back. The lipid spectrum across the study group improved, mostly without statistical significance. In obese diabetics the positive correlation between the therapeutic insulin dose and the total cholesterol level was found (p ¼ 0.007) before the weight reduction. Changes in non-cholesterol sterols and

Obese type 1 diabetics Before Skvalen (mmol/l) Lathosterol (mmol/l) Campesterol (mmol/l) B-sitosterol (mmol/l)

2.7  2.5 8.5  2.8

After a month After a year Controls 2.4  0.84 9.4  3.7

12.7  4.1 10.1  4.2 7.8  3.7

6.7  2.8

1.9  1.2 2.2  4.2  2.2 8.1  P ¼ <0.001 6.8  2.1 11.6  P ¼ <0.001 7.0  5.1 8.7 

0899-9007/$ - see front matter Ó 2012 Published by Elsevier Inc.

0.77 3.0 4.6 3.6

skvalen shows the table below. The data are presented as average  standard deviation. Conclusion: Weight reduction in obese type 1 diabetics was accompanied by lowering of therapeutic doses of insulin. A positive correlation between the therapeutic insulin dose and the total cholesterol level was found (p ¼ 0.007) in obese patients before weight reduction. A significant (p ¼ 0.001) fall of lathosterol and campesterol was revealed after the weight reduction, suggesting decreased endogenous synthesis of cholesterol and changes in cholesterol absorption. The study was funded by investigation programme of the Ministry of Industry and Trade of the Czech Republic 00179906, and investigation programme of the Ministry of Education, Youth and Sport 0021620820.

TREATMENT OF OBESITY BY CONTROLLED FASTING IN PATIENTS WITH TYPE 1 DIABETES MELLITUS EFFECT ON INSULIN SENSITIVITY AND GLUCOSE METABOLISM  F. Musil, A. Smahelová, R. Hyspler, A. Tichá, V. Bláha, L. Sobotka Department of Metabolic Care and Gerontology, Faculty of Medicine, love , Czech Charles University and University Hospital, Hradec Kra Republic Aims: The aim was to study the influence of 7 days of total fasting on insulin sensitivity and glucose metabolism in obese patients with type 1 diabetes mellitus (T1DM). Methods: We studied 14 obese patients with T1DM (42.6  9.4 years, BMI 32.4  2.1 kg m2) and 13 non-obese control patients with T1DM (36.9  13.9 years, BMI 22.6  2.1 kg m2). Insulin sensitivity was measured in obese T1DM patients before fasting, immediately after 7 days of fasting, as well as 21 days thereafter. The control group was studied only after overnight fasting. Insulin sensitivity was measured using a two-step hyperinsulinemic-euglycemic clamp lasting 6 hours; period 1: 0 to 120 minutes, 1 mU min1 kg1 of insulin; period 2: 120 to 360 minutes, 10 mU min1 kg1 of insulin. Glucose oxidation and nonoxidative glucose disposal were measured before and during the clamp by indirect calorimetry. Urinary urea nitrogen excretion was measured to calculate protein oxidation. Mean  SD, T-test, ANOVA were used for statistical evaluation. Results: Fasting T1DM patients lost 6.1  1.1 kg after the 7 days. Glycemia during fasting was maintained at 5 mmol/L by adjusting basal insulin doses. Fasting reduced insulin-mediated glucose disposal in both phases of the clamp (phase 1: from 5.18  1.43 to 2.96  0.49; phase 2: from 9.69  1.48 to 6.78  1.21 mg min1 kg1, P < 0.001). This was caused by reduced glucose oxidation after the fasting period (phase 1: from 1.55  0.64 to -0.01  0.56; phase 2: from 2.81  0.52 to 0.88  0.98 mg min1 kg1, P < 0.001). Non-oxidative glucose disposal was not changed.

Selected abstracts / Nutrition 28 (2012) 106–107

Conclusions: One week of fasting transiently decreased insulin-mediated glucose disposal in T1DM patients. This was caused by reduced glucose oxidation. To our knowledge, this is the first report describing this effect.

PERITONEAL DIALYSIS IMPROVES EARLY PROGNOSIS OF RENAL TRANSPLANT RECIPIENTS : ADIPOCYTOKINES AND MUSCLE METABOLISM 3  , Vladimır Teplan 1, Robert Gurlich 2, Ladislav Senolt 1  Vladimır Teplan jr 2, Milena Stollova 1 Dept of Nephrology, Transplant Center, Inst Clin Exp Medicine, Prague, 2 Dept of Surgery, Univ Hospital, Charles Univ 3rd School of Medicine, Prague, 3 Inst of Rheumatology, Charles Univ 1st School of Medicine, Prague

Peritoneal dialysis (PD) is superior to hemodialysis (HD) in stabilizing selected metabolic parameters in plasma and muscular tissue. In addition, some studies have confirmed that renal transplant patients on PD show better early development of kidney function and lower rates of post-transplant complications including cardiovascular ones. Our prospective randomized study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma and muscular/adipose tissue of renal transplant recipients originally treated by PD and HD. A total of 70 patients were on follow-up for 12 months. Of this number, 30 (Group I) were originally treated by PD and 40 (Group II) by HD. All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early post-transplant period) and did not differ statistically in terms of HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. Muscular and adipose tissue samples were obtained during transplantation. Assessment by magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) was performed in the area of abdominal and thigh muscles with subsequent MRI-TA and 1HMR analysis of intra-extracellular fat in the v m. tibialis ant. (CH3/CH2). At the end of the study period, there were significant differences between Groups I and II (t-test, ANOVA) in plasma: ADPN 20.30  10.2 vs 10.3  7.2 mg/ml, visfatin 1.09  0.62 vs 1.56  0.48 ng/ml, ADMA 3.60  0.47 vs 2.10  0.36 mmol/l; p < 0.01; leptin 55.6  10.2 vs 25.6  8.3 ng/l; p<0.01, respectively, and muscle examination (muscle/fat - visc/sc, mRNA expression), ADPN p<0.025; leptin p<0.01, resistin p < 0.02. Likewise, analysis of MRI and MRS findings revealed significant differences between Groups I and II; p<0.02, while assessment of renal function (Cin) showed higher glomerular filtration rates in Group I (p<0.02). Conclusion: Our study documented a beneficial metabolic effect of peritoneal dialysis on early development of renal transplant function together with a decrease in risk factors affecting post-transplant metabolic and cardiovascular complications. The study was supported by grant IGA NS 10529-3/2009.

A-FABP (A-FATTY-ACID BINDING PROTEIN) LEVELS IN CACHECTIC PATIENTS WITH ADVANCED HEAD AND NECK AND GIT CARCINOMAS L. Urbánek 1, P. Urbánková 2, M. Karpısek 3 I Surgical Clinic Faculty Hospital of St.Ann, Masaryk university Brno, 2 Clinic of Otorhinolaryngology and Head and Neck Surgery Faculty

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Hospital of St.Ann, Masaryk university Brno, 3 Farmaceutical Faculty of Human Farmacology and Toxicology Farmaceutic University Brno Introduction: Cancer cachexia syndrome is defined as a poor nutrition status in cancer patients developed due complicated interactions between tumorous mass and affected subject. This type of severe malnutrition is reported in 15-40% cancer patients in time of its clinical manifestation, but exact incidence is not known yet. Higher number of cachectic patients is reffered in pancreatic cancer (80%), about 60% patients with advanced lung cancer have severe involuntary weight loss in time of diagnosis. Weight loss leading to severe cachexia is very often detected in head and neck cancer (in 30-50% patients). Strong correlation between weight loss and poor prognosis was identified. Weight loss about 5% and more leads to the shortening of survival and worse outcomes of applied therapeutical modalities. Detail pathophysiology of cancer cachexia development is not identified yet, but complex multifactorial ethiology is obvious and influenced by net of pathological regulations. Complicated role of cytokines, hormones and neuropeptides and dysregulations in metabolic chains are newly described. Cancer cachexia syndrome is estimated to be chronic inflammatory status supported by higher activity of cytokines like TNF-a, IL-1b, IL-6 a INF-g. Higher cytokine levels are associated with shortening of survival in cachectic patients. Fatty acid-binding proteins (FABPs) are newly identified mediators associated with regulation of lipid and glucose metabolism. A-FABP (FABP4) is detected especially in adipose tissue and cytoplasm of macrophages. Animal studies describe its possible role in insulin resistance development. Higher plasmatic levels are reffered in obese, in female and patients with metabolic syndrome. As possible biomarker reflects lipolytic activity and general volume of adipose tissue. Material and methods: The primary object of our study was detection of A-FABP plasmatic levels in patients with cancer cachexia in the time of diagnosis before any oncological treatment. 79 patients with advanced head and neck and GIT tumours and concomitant involuntary weight loss 10% and more in the last six months were introduced to the study. A-FABP plasmatic levels were measured by enzyme-linked-immunosorbent assay. Associations with severity of weight loss and its time course constituted other studied paramethers and were statistically evaluated using non-parametric Spearmann correlation test. Results: Average A-FABP levels in study group were measured in range 43,403  46,710mg/l. Correlation between A-FABP levels and absolute and relative weight loss in patients with advanced GIT tumours and with period of weight decrease in advanced head and neck cancer were statistically significant (p < 0.05). Positive significant correlation was also detected between patients with advanced GIT malignities and absolute and relative weight loss per 1 month (p < 0.01). Conclusion: Identification of detail mechanisms of cancer cachexia syndrome is an important aim of many studies. Role of cytokines is clearly apparent but many new mediators are descibed. A-FABP levels were studied in association with atherosclerosis and metabolic syndrome but its analysis in cancer patients is not obvious.Significant correlation between weight loss and its dynamic changes and A-FABP levels reffered in our study can reflect lipolytic activity leading to elevated levels of free fatty acids and general reduction of fatty deposits in patients presenting cancer cachexia development. More studies will be needed to identify detail role of this group of mediators in cancer patients.