The effect of a vegetarian versus conventional hypocaloric diet on serum concentrations of persistent organic pollutants in patients with type 2 diabetes.

BACKGROUND AND AIMS: The aim of this study was to explore the effect of a vegetarian versus conventional diet on the serum levels of persistent organic pollutants (POPs) in patients with T2D after 12 weeks of dietary intervention and to assess their relationships with metabolic parameters. METHODS AND RESULTS: Men and women with T2D were randomly assigned to follow either a vegetarian diet without fish or meat (n = 37) or an isocaloric conventional antidiabetic diet (n = 37). Both diets were energy restricted (minus 500 kcal/day). All foods were provided to the participants. At randomization (week 0) and 12 weeks, the meal test was performed to assess the ß-cell function and serum levels of 24 POPs. Dioxins and dioxin-like POPs were analyzed by isotope dilution high-resolution gas chromatography (HRGC) and mass spectrometry after cleanup of the silica and carbon columns. Non-dioxin-like POPs were analyzed by gas chromatography with an electron capture detector (GC-ECD). Statistical analyses used were repeated-measures analysis of variance (ANOVA), a multivariate regression model, and Pearson's correlations. We observed a statistically nonsignificant trend toward increases in the serum levels of most POPs in response to both hypocaloric diets with no differences between groups. In the groups combined, the change in serum concentrations of total POPs was correlated to changes in HbA1c (r = +0.34; p < 0.01), fasting plasma glucose (r = +0.41; p < 0.01) levels, and ß-cell function measured as insulin secretion at a reference glucose level (r = -0.37; p < 0.01), independent of the changes in body weight and volume of visceral fat. CONCLUSION: Short-term hypocaloric vegetarian and conventional diets did not reduce the POP levels, possibly due to mobilization of fat stores. Our findings support the relationship between POPs and diabetes, especially ß-cell function. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00883038, completed.

Tagging rs10811661 variant at CDKN2A/2B locus is not associated with type 2 diabetes mellitus in Czech population.

Genome-wide association studies have resulted in the identification of the CDKN2A/2B locus as an important genetic determinant of type 2 diabetes mellitus development. The aim of this study was to investigate the role of this locus in the development of type 2 diabetes mellitus in Czech Slavonic population. Groups of 1,149 type 2 diabetic patients and a group of 2,312 healthy controls, both of Czech origin, were successfully genotyped for the rs10811661 CDK2A/2B tagging polymorphism. The "risky" TT genotype frequencies were almost identical in both examined groups (69.3 % in patients and 68.9 % in controls, P = 0.52; OR [95% CI] = 1.02 [0.87 - 1.19] for TT versus C allele carriers). Similar negative results were obtained when males (P = 0.93) and females (P = 0.23) were analysed separately. We have not confirmed the association between rs10811661 SNP and susceptibility to the type 2 diabetes mellitus in Czech Slavonic population.

[Diabetic retinopathy in the Czech National Diabetes Programme 2012-2022]. / Diabetická retinopatie v národním diabetologickém programu 2012-2022.

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in people of working age. In the Czech Republic, the number of patients with diabetic retinopathy is still increasing as well as the number of diabetic patients. It is known, that the comprehensive preventive and therapeutic procedures reduce the risk of visual loss by more than 90%. These procedures include intervention of modifiable risk factors (especially hypertension and hyperglycaemia), active screening of DR and specialized ophthalmologic treatment. The Czech National Diabetes Programme 2012-2022, which is built on similar initiatives as in 1984 and 2000, has been completed in late 2012. Its main goal is to improve the health outcomes for people diabetes in the Czech Republic. The programme includes specific procedures aimed at improvement of organization and treatment providing to patients with diabetic retinopathy.

[A recommended approach to evaluate cardiovascular risk and to prevent cardiovascular diseases and type 2 diabetes mellitus in women with polycystic ovary syndrome]. / Doporucený postup k posouzení kardiovaskulárního rizika a prevenci kardiovaskulárních onemocnení a diabetes mellitus 2. typu u zen se syndromem polycystických ovarií

Polycystic ovary syndrome is one of the most common endocrinopathy in women of fertile age. It is commnoly accompanied by an increased occurence of cardiovascular risk factors. This association led to a consensus statement of Androgen Excess Society for screening of cardiovascular risk factors. We present the recommendations of Czech Endocrine and Czech Diabetological Societies for the screening and primary prevention of cardiovascular diseases and diabetes mellitus.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes.

AIMS: The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. METHODS: A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. RESULTS: Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. CONCLUSIONS: A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

Selected adipokines - plasma concentrations and adipose tissue expressions during 24-hour lipid infusion in healthy men.

Our aim was to assess the reaction of TNFalpha, resistin, leptin and adiponectin to lipid infusion. Eight healthy subjects underwent a 24-hour lasting infusion of lipid emulsion. Plasma concentrations and expressions of selected cytokines in subcutaneous fat were measured. TNFalpha plasma concentration did not change during the first 4 hours of hypertriglyceridemia, but a significant increase after 24 hours was detected (p<0.001 for 0; 30; 240 min vs. 24 h). Plasma concentration of resistin significantly increased at 30 min of infusion and remained elevated (p<0.01 for 0 min vs. 30; 240 min; p<0.001 for 0 min vs. 24 h). Plasma concentrations of leptin and adiponectin did not show any significant changes. Although the expression of resistin in the subcutaneous adipose tissue tended to increase, the change was not significant. Expressions of TNFalpha, leptin and adiponectin were unaffected. In conclusions, our results indicate that acutely induced hyperlipidemia could influence the secretion of TNFalpha and resistin.

[Treatment of diabetes in metabolic syndrome]. / Lécba diabetu pri metabolickém syrndromu.

Hyperglycaemia is a typical feature of metabolic syndrome (MeTS) and one of its independent diagnostic criteria. The term includes impaired glucose homeostasis (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus. Although glycaemic control has been shown to lower the risk of microvascular events, the effect of intensive glycaemic control on macrovascular outcomes is less clear. Epidemiological studies show hyperglycaemia, particularly the postprandial one, to be a clear risk factor for cardiovascular (CV) mortality and morbidity. However, the intervention studies are less conclusive. The large interventional studies published in 2008 and 2009 (UKPDS, VADT, ACCORD, ADVANCE, RECORD) advocate the controlling of nonglycemic risk factors (through blood pressure control, lipid lowering with statin therapy, aspirin therapy, and lifestyle modifications) as the primary strategies for reducing the burden of CV disease in people with diabetes, and demonstrated the need for individualized approach to the patients' care in terms of blood glucose control. The patients with shorter duration of type 2 diabetes and without established atherosclerosis might reap CV benefit from intensive glycemic control. Conversely, it is possible that potential risks of intensive glycaemic control (hypoglycaemia) may outweigh its benefits in other patients, such as those with a very long duration ofdiabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty. According to the latest recommendations of the Czech Diabetes Society that are in line with the European and US standards the best way to protect type 2 diabetic patients against coronary and cerebrovascular disease is to target all cardiovascular risk factors (blood pressure treatment, including lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors hypertension, dyslipidemia, obesity and other symptoms of metabolic syndrome. The target HbA1c levels in patients with the low CV risk shoul be below 4.5%. Less strict goals (HbA1c below 6%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with long-standing diabetes. The individual targets should be achieved safely (without hypoglycaemias). Slow advancing in diabetes compensation is preferred. Lifestyle changes are the cornerstone of therapy. Metformin is the drug of choice; its administration, together with lifestyle changes, should be initiated immediately after the diagnoses of diabetes. If monotherapy does not provide satisfactory glucose control, other oral antidiabetic agents or insulin are added to the combination. Since it is not known which hypoglycaemic agents are beneficial from the perspective of long-term patient prognosis, the selection is liberal. Contraindication of the various farmaceuticals must be respected. It is possible to use a range of different combinations, metformin is administered with a glitazone (zero risk of hypoglycaemias is the advantage) with sulphonylurea derivatives (low price is the advantage) with glinides, with incretins, acarbose, antiobesity agents or insulin. The next step is a triple combination of hypoglycaemic agents with different mechanisms of action. Therapy also includes education focusing on changes to dietary and lifestyle habits, including smoking cessation, and education related to the prevention of complications, with particular regard to prevention of diabetic foot and atherosclerosis.

Urinary urea nitrogen excretion during the hyperinsulinemic euglycemic clamp in type 1 diabetic patients and healthy subjects.

The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry (IC) is used for estimation of insulin-stimulated substrate utilization. Calculations are based on urinary urea nitrogen excretion (UE), which is influenced by correct urine collection. The aims of our study were to improve the timing of urine collection during the clamp and to test the effect of insulin on UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11). Urine samples were collected (a) over 24 h divided into 3-h periods and (b) before and during two-step clamp (1 and 10 mIU.kg(-1).min(-1); period 1 and period 2) combined with IC. The UE during the clamp was corrected for changes in urea pool size (UEc). There were no significant differences in 24-h UE between C and DM1 and no circadian variation in UE in either group. During the clamp, serum urea decreased significantly in both groups (p<0.01). Therefore, UEc was significantly lower as compared to UE not adjusted for changes in urea pool size both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp, UEc decreased significantly in both groups (p<0.01). UEc during the clamp was significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2 (p<0.01). The UE over 24 h and UEc during the clamp were statistically different in both C and DM1. We conclude that urine collection performed during the clamp with UE adjusted for changes in urea pool size is the most suitable technique for measuring substrate utilization during the clamp both in DM1 and C. Urine collections during the clamp cannot be replaced either by 24-h sampling (periods I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease in UEc in DM1 implicates the impaired insulin effect on proteolysis.

Biologically active polyamines in pig kidneys and spleen: Content after slaughter and changes during cold storage and cooking.

Polyamines putrescine, spermidine (SPD) and spermine (SPM) were determined as dansyl derivatives using an HPLC method. Distribution of SPD and SPM in pair kidneys was homogenous. The mean SPD and SPM contents in pig kidneys 24h after slaughter were 9.39±3.35 and 53.1±14.0mgkg(-1), respectively with no significant differences between barrows and gilts. Putrescine content was below the detection limit of 1.2mgkg(-1). In kidneys stored aerobically or vacuum-packaged at 2-3°C for 7 and 21 days, respectively, SPD and SPM decreased significantly. Stewing decreased both polyamines more extensively in kidneys processed on day-1 after slaughter than on day-7 after storage at 2-3°C. The mean SPD and SPM in 10 spleens 24h after slaughter were 36.7±5.70 and 34.0±7.64mgkg(-1), respectively. Thus, both pork kidney and spleen are foods with a high level of SPM and SPD.

The identification and simultaneous quantification of neuroactive androstane steroids and their polar conjugates in the serum of adult men, using gas chromatography-mass spectrometry.

Certain androstane steroids (AS) modulate ionotropic receptors, as do the pregnane steroids. Whereas women produce significant amounts of neuroactive progesterone metabolites, the steroid neuromodulators in men originate mainly from the 3-oxo-4-ene C(19)-steroids, which are converted to their 3alpha- and 3beta-hydroxy-5alpha/5beta-reduced metabolites. The neuromodulating effects of AS prompted us to monitor circulating levels of the steroids to estimate metabolic pathways in the periphery that may influence brain concentrations of AS. Hence, the serum levels of 20 steroids and 16 steroid polar conjugates including 17-oxo- and 17beta-hydroxy-derivatives of 5alpha/beta-androstane-3alpha/beta-hydroxy-androstane steroids were quantified in 15 men (16-62 years of age) using GC-MS. The conjugated AS for the most part reached micromolar concentrations, these being two or three orders of magnitude higher than those of the free steroids. The ratios of conjugates to free steroids were one to two orders of magnitude higher than the values for the corresponding pregnane steroids. This data suggested that conjugation may considerably restrain the transport of free AS from the periphery into the central nervous system.

Changes in the content of biologically active polyamines during storage and cooking of pig liver.

Dietary polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) participate in numerous human physiological processes, including tumour growth. Eight experiments with pig liver were carried out. In two, livers were stored at -18°C for 168 days, in four, livers were stored aerobically (AE), vacuum-packaged (VP) and packaged in a modified atmosphere (MO; 70% N(2) and 30% CO(2), v/v) at +2°C for 9, 21 and 21 days, respectively, and in two, the effects of four cooking treatments were tested. Polyamines were determined as dansyl derivatives using an HPLC method. Distribution of both SPD and SPM in the four main liver lobes was homogenous. The initial SPD and SPM contents in 14 livers 24h after slaughter were 23.3±6.7 and 94.5±19.6mgkg(-1), respectively. The putrescine content was below the limit of detection. The content of SPD and SPM decreased during frozen-storage to about 70% of the initial values. On day-9 of storage, mean SPD and SPM contents decreased to about 85% of the initial values in livers stored in MO and to about 75-80% in AE and VP at 2°C. The decrease continued more extensively in VP than in MO. PUT was detected from day-15 of VP and MO storage. There was a significant decrease in SPD and SPM, to about 70-60% of the initial content during cooking.

[Pathogenesis of diabetic retinopathy]. / Patogeneze diabetické retinopatie.

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increased polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other metabolic and haemodynamic factors influencing numbers of intracellular signalling molecules such as PKC, MAPK or NF-kappaB. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, vasoactive agents, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant patterns, and finally in angiogenesis and tissue remodelling. The insights into pathophysiological mechanisms responsible for DR that are presented here could help in the development of a more targeted approach to its prevention and treatment.

[The effect of treatment with fenofibrate on the risk profile of patients with metabolic syndrome and mixed dyslipidemia treated on an outpatient basis]. / VIiv lécby fenofibrátem na rizikový profil nemocných s metabolickým syndromem a smísenou dyslipidemií lécených ambulantne.

The study has shown that patients with metabolic syndrome and typical dyslipidemia treated on an outpatient basis by general practitioners or specialists are those whose anamneses include IHD or diabetes and who are very often indicated for combined statin-fibrate therapy. Fenofibrate therapy combined with a single lifestyle intervention in the form of individual interview resulted in the following improvement of the risk profile of the above patients: significant decrease in body weight and waist circumference, decrease in blood pressure and fasting glycemia; improvement of typical dyslipidemia in 90% of patients, however, only 30% of patients achieved the target TG levels below 1.7 mmol/l and the HDL-cholesterol levels above 1.3 mmol/l and 1 mmol/l in women and men, respectively. A total of 60% of patients no longer met the criteria for MS after 6 months of therapy. However, LDL-cholesterol and total cholesterol levels in patients with IHD or with diabetes were very unsatisfactory; only 6% of patients had achieved the recommended level of target LDL-cholesterol below 2.5 mmol/l before the intervention, i.e. 94% of the patient sample was indicated for statin therapy. 86% of patients with LDL-cholesterol above 2.5 mmol/l remained in our patient sample after non-pharmacological and pharmacological fibrate therapy. The results show that combined statin--fibrate therapy would be the best therapy for patients with IHD or diabetes who meet the MS criteria and whose typical dyslipidemia is expressed.

Content of biologically active polyamines in livers of cattle, pigs and chickens after animal slaughter.

Dietary polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) participate in an array of important human physiological roles, including tumour growth. Physicians and dieticians thus need reliable information on polyamine contents in foods. However, data for livers are lacking. We determined therefore the content of these polyamines 24h after slaughter in livers of young bulls, cows, pigs and chicken in 58, 19, 36 and 38 samples, respectively. Polyamines were determined as N-benzamides by micellar electrokinetic capillary chromatography. Mean PUT contents about 25mgkg(-1) were found in cattle livers, while very low or negligible contents were determined in livers of the other animals. Extremely high mean SPD contents of 122 and 161mgkg(-1) were found in livers of bulls and cows, respectively and mean levels of 32 and 57mgkg(-1) in livers of pigs and chicken. An opposite relation was observed for SPM. Its mean contents were 43, 35, 115 and 120mgkg(-1) for bulls, cows, pigs and chicken livers, respectively. Thus, livers of the tested animal species belong among foods with the highest polyamine contents. However, the contents ranged very widely, that makes application of the results for the control of human nutrition rather difficult. Polyamine contents in bovine blood were found to be below the detection limits of 2.1, 1.0 and 1.4mgkg(-1) for PUT, SPD and SPM, respectively. Thus, the blood content did not contribute to the substantial polyamine contents in bovine liver found in this study.

Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans.

OBJECTIVE: Nitric oxide (NO) may contribute to the actions of angiotensin converting enzyme (ACE) inhibitors. In contrast, angiotensin type 1 (AT1) receptor blockers (AT1B) have been considered to act exclusively by inhibiting angiotensin II actions. However, recent experimental findings suggest that AT1B actions may be also partly mediated by NO. In this study, we explored whether ACE inhibitors and AT1B modulate hemodynamic responses to L-arginine (L-arg), a NO precursor. METHODS: Systemic (Finapres) and renal hemodynamic responses to L-arg (200 mg/kg body weight), associated with markers of systemic and renal NO production, were assessed before (control) and after 3 weeks of randomized pretreatment with the ACE inhibitor ramipril (5 mg/day for 3 weeks) or the AT1B losartan (50 mg/day for 3 weeks) in nine healthy male subjects (33 +/- 2 years; body mass index 25.5 +/- 0.5 kg/m2). RESULTS: Control L-arg did not influence mean arterial pressure (MAP) (92 +/- 5 versus 90 +/- 5 mmHg; not significant). In contrast, L-arg decreased MAP when administered after pretreatment with ramipril (89 +/- 5 versus 83 +/- 4 mmHg; P< 0.01) or losartan (90 +/- 44 versus 86 +/- 4; P< 0.05). Control L-arg infusion had no effect on renal plasma flow (RPF) (paraminohippuric acid clearance) and renal vascular resistance (RVR), whereas the glomerular filtration rate (GFR) (inulin clearance) decreased (98 +/- 4 versus 89 +/- 5 ml/min; P< 0.05), resulting in a decrease in filtration fraction (P< 0.05). After ramipril, L-arg induced renal vasodilation as indicated by significant changes in RPF (576 +/- 41 versus 669 +/- 21 ml/min; P< 0.01) and RVR (P< 0.05). The GFR did not change statistically after ramipril pretreatment (91 +/- 3 versus 97 +/- 4 ml/min; not significant); however, the trend was different as compared with control (F= 5.7, P < 0.05). L-Arg-induced renal vasodilation was also observed after losartan (RPF, 637 +/- 34 versus 706 +/- 40 ml/min; P< 0.05). Enhanced renal and systemic responses to L-arg after ACE inhibitor and AT1B were associated with a rise in plasma L-citrulline levels, which was greater than after control L-arg (P < 0.05). However, other indicators of NO activity such as plasma and urinary cyclic guanosine 3',5'-monophosphate, and nitrates, remained unchanged throughout all experiments. CONCLUSION: The results indicate that ACE inhibitors and AT1B have a potential to enhance L-arg-induced vasodilation both in systemic and renal vascular beds. However, these hemodynamic responses were not associated with convincing changes in indicators of systemic or renal NO activity, suggesting a contribution of NO-independent vasodilator mechanisms.

Metabolic effects of omega-3 fatty acids in type 2 (non-insulin-dependent) diabetic patients.

The metabolic effects of a 3-week dietary supplement of a fish oil concentrate was examined in mildly obese, normotriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents (n = 20). Patients were randomized into two groups, receiving 15 ml per day of fish oil (Martens Oil, Norway) containing 3.1 g of omega-3 fatty acids (FA) (n = 10) or placebo (n = 10). Whereas fish oil led to the expected increase in the ratio of omega-3 to omega-6 FA in serum phospholipids, reflecting the increase in omega-3 FA intake, it did not alter fasting or mixed meal stimulated blood glucose, plasma insulin, and C-peptide concentrations. No changes in insulin action were noted, estimated by the metabolic clearance rates of glucose at plasma insulin levels of approximately 100 microU/ml and 1,400 microU/ml during a hyperinsulinemic, isoglycemic clamp; no changes were seen in insulin binding to erythrocytes. We conclude that during short-term administration, no adverse effects of low dose fish oil on glucose homeostasis were found in mildly obese NIDDM patients treated with oral hypoglycemic agents.

Serum phospholipid fatty acid composition and insulin action in type 2 diabetic patients.

Relationships have been demonstrated between insulin sensitivity and the fatty acid (FA) composition of serum and tissue lipids in adult humans. The present study aimed to investigate the above relationships in different groups of type 2 diabetic patients (DM2). The FA composition of serum phospholipids (S-PL) measured by gas liquid chromatography and insulin action during a 2-step hyperinsulinemic isoglycemic clamp (1 and 10 mU/kg. min) were determined in 21 newly diagnosed DM2 subjects (DMN), in groups of long-term DM2 patients treated with hypoglycemic agents (DMH; n = 21) or diet alone (DMD; n = 11), and in 24 healthy subjects (HS). In diabetics, the metabolic clearance rates of glucose at both insulin levels (MCR(glu)submax and MCR(glu)max) were significantly reduced compared with HS (MCR(glu)submax DMN, 5.35 +/- 2.7 mL x kg(-1) x min(-1), DMH, 5.38 +/- 2.17 mL x kg(-1) x min(-1); DMD, 5.48 +/- 2.35 mL x kg(-1) x min(-1) v HS, 10.9 +/- 3.3 mL x kg(-1) x min(-1); P <.01; MCR(glu)max DMN, 13.3 +/- 3.3 mL x kg(-1) x min(-1); DMH, 12.5 +/- 3.0 mL x kg(-1) x min(-1); DMD, 13.3 +/- 3.0 mL x kg(-1) x min(-1) v HS, 17.4 +/- 3.8 mL x kg(-1) x min(-1); P <.05). Increased contents of highly unsaturated n-6 family FA (P <.01), arachidonic acid in particular (DMN, 10.98% +/- 1.79%; DMD, 10.78% +/- 1.64%; DMH, 10.97% +/- 1.7% v HS, 8.51% +/- 1.53%; P <.001), were found in all groups of diabetics compared with HS, while lower levels of linoleic acid were seen in DMN (P <.001) and DMH (P <.05). The contents of saturated FA and monounsaturated FA were comparable in HS, DMN, and DMD. While in HS there were significant negative correlations between MCR(glu) and the contents of saturated FA and a positive association between insulin action and proportions of linoleic and arachidonic acids, no significant relationships were found in diabetic subjects. Different groups of DM2 patients show an altered FA pattern of S-PL, which is not related to insulin action. The above data support the hypothesis that changes in FA composition may play a role in modulating insulin action in peripheral tissues, but cannot explain the insulin resistance (IR) in DM2 patients.

Fatty acid composition of serum lipids and erythrocyte membranes in type 2 (non-insulin-dependent) diabetic men.

The fatty acid (FA) composition of serum lipids and erythrocytes was studied in 21 men with non-insulin-dependent diabetes mellitus (NIDDM) and in 14 normal subjects matched for age, sex, body weight, and dietary intake. Lower levels of linoleic acid and higher levels of highly unsaturated FA (daughter) of n-3 and n-6 family FA, reflected in a higher unsaturation index, were found in serum phospholipids (S-PL), in phospholipids of erythrocyte membranes (ery-PL), and in serum cholesterolesters (S-CHE). The unsaturation index of serum phospholipids significantly correlated with glycosylated hemoglobin A1c (P less than .05) and blood glucose levels after glucose load (P less than .001). The results suggest that elongation and desaturation of essential FA (linoleic acid in particular) are increased. The above changes may be associated with accelerated atherosclerosis in type 2 diabetics.