Perfused capillary surface area in postural and locomotor skeletal muscle

A measure was made of the perfused capillary surface area per gram of tissue (S_f) in postural, anterior latissimus dorsi (ALD), and locomotor, posterior latissimus dorsi (PLD), skeletal muscles in chickens. The animals were anesthetized with L.A. Thesia and the ALD and PLD muscles were prepared for observation using a modification of the method developed by R. E. Klabunde and P. C. Johnson (1977, Amer. J. Physiol.232, H411–417). S_f was determined from the relationship S_f = πdLθ_f, where d = capillary diameter, L = capillary length, and θ_f = number of perfused capillaries per gram. Capillary lengths and diameters were measured directly through the microscope. Estimates of θ_f were measured in two ways: by a flow method (θ^Q_f), and by an histochemical method (θ^H_f). It was observed that the average capillary diameter in PLD was the same as in ALD muscles, but the average capillary length in PLD was two times longer than in ALD muscles. Both the flow and histochemical methods yielded values of θ_f that gave similar values of S_f for PLD muscles (S^Q_f = 24.7 ± 20.0 cm²/g, S^H_f = 13.7 ± 14.4 cm²/g), but different values for ALD muscles (S^Q_f = 9.8 ± 6.8 cm²/g, S^H_f = 42.8 ± 19.1 cm²/g). The difference between S^Q_f and S^H_f for ALD muscles could be explained by the more irregular and longer perfusion path observed in postural versus locomotor muscle. The flow method appears to underestimate S_f in capillary beds with irregular perfusion paths. The results indicate that only a small fraction of the total capillary bed was perfused in resting skeletal muscle and that S^H_f for ALD was approximately three times larger than S^H_f for PLD.     

Decreased beta-adrenergic sensitivity in insulin-dependent diabetic subjects

To study beta-adrenergic sensitivity in diabetes mellitus, we performed isoproterenol sensitivity tests in 34 insulin-dependent diabetic patients and 10 age-matched normal subjects. beta-adrenergic sensitivity [defined as the dose of isoproterenol required to increase the resting heart rate by 25 beat/min, (I25)] was significantly higher in the diabetic group (4.07 +/- 1.4 micrograms, mean +/- SD) than in the normal group (2.02 +/- 1.49 micrograms). A comparison of I25 of normal subjects and diabetic patients as a function of age showed that the latter were significantly less sensitive to beta-adrenergic stimulation at all ages (P less than 0.01). In diabetic patients, beta-adrenergic sensitivity also increased with the duration of diabetes (r = 0.64, P less than 0.0005), but the correlation was stronger when the age of the patients and the duration of the diabetes were both taken into consideration (r = 0.72, P less than 0.0005). We conclude that beta-adrenergic sensitivity is diminished in patients with type I diabetes mellitus of all ages.     

Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects

BACKGROUND: In type 2 diabetes, metformin reduces cardiovascular risk beyond the effect of glycaemic control. Since oxidative stress and the consequent enhanced platelet activation contribute to accelerated atherosclerosis in diabetes, we hypothesized that metformin could reduce oxidative stress in this condition. METHODS: We randomized 26 newly diagnosed type 2 diabetic subjects to assume either metformin (M, n = 13) or gliclazide (G, n = 13) for 12 weeks. Drugs were titrated as needed to achieve good glycaemic control. Before and after treatment, we determined blood glucose, insulin, HbA(1c), vitamin A and E levels and 8-iso-PGF(2alpha) and 11-dehydro-thromboxane B(2) urinary excretion, an in vivo oxidative stress and a thromboxane-dependent platelet activation marker, respectively. RESULTS: Notwithstanding a comparable improvement in metabolic control, 8-iso-PGF(2alpha) (M from 708 +/- 32 to 589 +/- 45 pg/mg cr, p < 0.001; G from 646 +/- 80 to 665 +/- 79, pg/mg cr, p = ns) and 11-dehydro-thromboxane B(2) (M from 2190 +/- 196 to 1753 +/- 150 pg/mg cr, p < 0.05; G from 2048 +/- 202 to 1923 +/- 223, pg/mg cr, p = ns) urinary excretion decreased after metformin but not after gliclazide treatment. After metformin, vitamin A and E levels significantly increased while they remained unchanged after gliclazide. CONCLUSIONS: These data suggest that metformin could improve oxidative stress, preserve antioxidant function and restrain platelet activation in type 2 diabetes.     

Antihyperglycemic effects of stevioside in type 2 diabetic subjects

Stevioside is present in the plant Stevia rebaudiana Bertoni (SrB). Extracts of SrB have been used for the treatment of diabetes in, for example, Brazil, although a positive effect on glucose metabolism has not been unequivocally demonstrated. We studied the acute effects of stevioside in type 2 diabetic patients. We hypothesize that supplementation with stevioside to a test meal causes a reduction in postprandial blood glucose. Twelve type 2 diabetic patients were included in an acute, paired cross-over study. A standard test meal was supplemented with either 1 g of stevioside or 1 g of maize starch (control). Blood samples were drawn at 30 minutes before and for 240 minutes after ingestion of the test meal. Compared to control, stevioside reduced the incremental area under the glucose response curve by 18% (P =.013). The insulinogenic index (AUC(i,insulin)/AUC(i,glucose)) was increased by approximately 40% by stevioside compared to control (P <.001). Stevioside tended to decrease glucagon levels, while it did not significantly alter the area under the insulin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide curves. In conclusion, stevioside reduces postprandial blood glucose levels in type 2 diabetic patients, indicating beneficial effects on the glucose metabolism. Stevioside may be advantageous in the treatment of type 2 diabetes.     

Metabolic effects of muraglitazar in type 2 diabetic subjects

Aim: To assess the effect of muraglitazar, a dual peroxisome proliferator‐activated receptor (PPAR)γ‐α agonist, versus placebo on metabolic parameters and body composition in subjects with type 2 diabetes mellitus (T2DM). Methods: Twenty‐seven T2DM subjects received oral glucose tolerance test (OGTT), euglycaemic insulin clamp with deuterated glucose, measurement of total body fat (DEXA), quantitation of muscle/liver (MRS) and abdominal subcutaneous and visceral (MRI) fat, and then were randomized to receive, in addition to diet, muraglitazar (MURA), 5 mg/day, or placebo (PLAC) for 4 months. Results: HbA1c_c decreased similarly (2.1%) during both MURA and PLAC treatments despite significant weight gain with MURA (+2.5 kg) and weight loss with PLAC (?0.7 kg). Plasma triglyceride, LDL cholesterol, free fatty acid (FFA), hsCRP levels all decreased with MURA while plasma adiponectin and HDL cholesterol increased (p < 0.05–0.001). Total body (muscle), hepatic and adipose tissue sensitivity to insulin and β cell function all improved with MURA (p < 0.05–0.01). Intramyocellular, hepatic and abdominal visceral fat content decreased, while total body and subcutaneous abdominal fat increased with MURA (p < 0.05–0.01). Conclusions: Muraglitazar (i) improves glycaemic control by enhancing insulin sensitivity and β cell function in T2DM subjects, (ii) improves multiple cardiovascular risk factors, (iii) reduces muscle, visceral and hepatic fat content in T2DM subjects. Despite similar reduction in A1c with PLAC/diet, insulin sensitivity and β cell function did not improve significantly.     

Efficacy of glimepiride in Japanese type 2 diabetic subjects

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% (p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change (p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI > or = 25) or had a high HOMA-IR (HOMA-IR > or = 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI ( > or = 25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.     

In vivo sequential study of skeletal muscle capillary permeability in diabetic rats: effect of anthocyanosides

Alterations in the capillary filtration of macromolecules are well documented in diabetic patients and experimental diabetes. Various flavonoids including anthocyanosides and ginkgo biloba extracts have been shown to be effective against experimentally induced capillary hyperfiltration. The aim of the present study was to test the effects of anthocyanosides on capillary filtration in diabetic rats. For this purpose, we have validated the use of our previously described in vivo method for measurement of the capillary filtration of albumin (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium myrtillus (group B), or no treatment (group C). The isotopic test of CFA consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing venous compression on a hindquarter, and measuring radioactivity externally on the limb before, during, and after removal of venous compression. After removal of the tourniquet, the radioactivity curve decreased. Interstitial albumin retention (AR) and the ratio of the amplitudes of the low- and high-frequency peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier transform of the last part of the radioactivity curve, were calculated. In STZ-treated animals, the isotopic test was performed at a mean age of 97 days (time 1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12 weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic groups than in the control rats, without a significant difference between these groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In group C, AR increased significantly (P < .0005) from time 1 to time 3. In group A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the LF/HF ratio significantly increased with time (P < .0005) and the levels at time 3 were significantly higher versus control rats (P < .0001). In group B, the LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values found in the control rats. In conclusion, these data show that (1) this new in vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic rats, (2) it is reproducible and may be repeated over several months to evaluate spontaneous microcirculatory changes, and (3) anthocyanosides appear to be effective in preventing the increase in CFA and the failure of lymphatic uptake of interstitial albumin in diabetic animals.     

Decreased dipeptidyl peptidase-IV activity and glucagon-like peptide-1(7-36)amide degradation in type 2 diabetic subjects

Dipeptidyl peptidase (DPP-IV) rapidly metabolizes hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) <7%, upper limit of non-diabetic range), moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HbA(1c) >9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5+/-0.7 nmol/ml/min (n=70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1+/-0.7 nmol/ml/min (p<0.001, n=54). DPP-IV activity was negatively correlated with both glucose (p<0.01) and HbA(1c) (p<0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p<0.01, n=25), 1.3-fold (p<0.001, n=19) and 1.3-fold (p<0.05, n=10) in good, moderate and poorly controlled diabetic groups, 18.7+/-1.0, 17.4+/-1.4 and 18.0+/-1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control.     

Increased capillary permeability to albumin and diabetic neuropathy

An increase in the capillary permeability to albumin (CPA) has been reported in diabetic patients. We observed this frequently with a non-invasive isotopic test derived from the Landis method, using 99mTc-albumin and measuring residual radioactivity externally after removal of forearm venous compression. Evidence of the independent effects of hypertension and microangiopathy on CPA has already been found. The present work was designed to investigate CPA using the same test on diabetic patients without retinopathy and clinical proteinuria. Some of these patients had objective clinical distal and symmetrical polyneuropathy. Neuropathy was clearly present in 10 of the 11 patients with an abnormal test unexplained by causes other than diabetes and in only one of the 17 patients with a normal test. The most frequent abnormality affected the late radioactivity disappearance curve, which probably reflects an impaired lymphatic wash-out of interstitial albumin. These results strongly suggest a link between peripheral neuropathy and diabetic functional microangiopathy. An elevated blood flow secondary to sympathetic nerve failure may induce an increase in CPA and a saturation of lymphatic pumping which could also be deficient due to impaired lymphatic innervation.     

Under-utilization of capillary glucose monitoring by type 2 diabetic patients

OBJECTIVES: Postprandial glycemic excursions contribute significantly to A1C level. Furthermore, postprandial plasma glucose (PPG) is an independent risk factor for cardiovascular disease. We have evaluated the frequency of monitoring and the level of PPG in type 2 diabetic patients followed by their family physician. PATIENTS AND METHODS: Canadian multicenter observational study, including 185 type 2 diabetic patients. Capillary blood glucose was measured with an Ultrasmart glucose meter (Life Scan) during a routine visit to their general practitioner. The patients also had to answer a questionnaire concerning the time since their last meal before the visit, and the frequency of postprandial monitorings defined as 10 mmol/L). A PPG >10 mmol/L was found in 18.8% (n=9), 43.5% (n=47) and 73.1% (n=19) of patients in Groups 1-3, respectively. Independent of treatment category, the mean (S.D.) PPG measured by capillary methods was above the recommended target: 10.6 mmol/L (3.7) <1-h postprandial; 10.0 mmol/L (4.2) between 1 and 2h postprandial meal; and 9.9 (3.9) 2 and 3h after meal. CONCLUSION: This observational study shows that a third of the patients measured their PPG and for those who did, only a third were within the recommended target. It suggests that the patients, and probably the treating physicians, are not aware of the importance of measuring PPG. Continued medical education strategies are required to implement the recommendations for measuring and treating PPG as part of the intensive treatment of diabetes.     

Insulin resistance is associated with impaired nitric oxide synthase activity in skeletal muscle of type 2 diabetic subjects

Type 2 diabetes is an insulin-resistant state characterized by hyperinsulinemia and accelerated atherosclerosis. In vitro and in vivo studies in rodents have suggested that nitric oxide generation plays an important role in glucose transport and insulin action. We determined nitric oxide synthase (NOS) activity in skeletal muscle of 10 type 2 diabetic (hemoglobin A(1C) = 6.8 +/- 0.1%) and 11 control subjects under basal conditions and during an 80 mU/m(2).min euglycemic insulin clamp performed with vastus lateralis muscle biopsies before and after 4 h of insulin. In diabetics, insulin-stimulated glucose disposal (Rd) was reduced by 50%, compared with controls (5.4 +/- 0.3 vs. 10.4 +/- 0.5 mg/kg.min, P < 0.01). Basal NOS activity was markedly reduced in the diabetic group (101 +/- 33 vs. 457 +/- 164 pmol/min.mg protein, P < 0.05). In response to insulin, NOS activity increased 2.5-fold in controls after 4 h (934 +/- 282 pmol/min.mg protein, P < 0.05 vs. basal), whereas insulin failed to stimulate NOS activity in diabetics (86 +/- 28 pmol/min.mg protein, P = NS from basal). Basal NOS protein content in muscle was similar in controls and diabetics and did not change following insulin. In controls, insulin-stimulated NOS activity correlated inversely with fasting plasma insulin concentration (r = -0.58, P = 0.05) and positively with Rd (r = 0.71, P = 0.03). In control and diabetic groups collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.52, P = 0.02). We conclude that basal and insulin-stimulated muscle NOS activity is impaired in well-controlled type 2 diabetic subjects, and the defect in insulin-stimulated NOS activity correlates closely with the severity of insulin resistance. These results suggest that impaired NOS activity may play an important role in the insulin resistance in type 2 diabetic individuals.     

Effects of exercise on inflammation markers in type 2 diabetic subjects

Endothelial dysfunction and plasma markers of inflammation are significantly increased in type 2 diabetics. Several proinflammatory cytokines, acute-phase proteins, and cell adhesion molecules, such as C-reactive protein (CRP), interleukines (IL), and tumor necrosis factor alpha (TNF-α), seem to play a role in the low-grade systemic inflammation observed in these subjects. Lifestyle changes are necessary to prevent atherosclerosis and cardiovascular events. Physical exercise is known to reduce markers of inflammation by decreasing adipocytokine production and cytokine release from skeletal muscles, endothelial cells, and immune system and also improving antioxidant status. In type 2 diabetics, aerobic and resistance training have different effects on cytokine levels, and the differences in the modalities of exercise (type, duration, and intensity) and especially in the examined population could produce different results. Recent research showed that combined exercise has greater anti-inflammatory effects than aerobic or resistance exercise alone causing a deepest decrease in CRP, IL-6, IL-1β, TNF-α, leptin, and resistin and a higher increase in anti-inflammatory cytokines such as IL-4, IL-10, and adiponectin.     

Islet amyloid polypeptide in pancreatic islets from type 2 diabetic subjects

Aims/hypothesis: Islet amyloid polypeptide (IAPP) is a chief constituent of amyloid deposits in pancreatic islets, characteristic histopathology for type 2 diabetes. The goal of this study was to analyze islet cell composition in diabetic islets for the process of transforming water-soluble IAPP in β-cells to water-insoluble amyloid deposits by Immunocytochemical staining using different dilutions of anti-IAPP antibody. IAPP in β-cell granules may initiate β-cell necrosis through apoptosis to form interstitial amyloid deposits in type 2 diabetic islets.

Results: Control islets revealed twice as much β-cells as α-cells whereas 15 of 18 type 2 diabetic cases (83%) revealed α- cells as major cells in larger islets. Diabetic islets consisted of more larger islets with more σ-cells than β-cells, which contribute to hyperglucagonemia. In control islets, percentage of IAPP-positive cells against β-cells was 40–50% whereas percentage for type 2 diabetic islets was about 25%. Amyloid deposits in diabetic islets were not readily immunostained for IAPP using 1: 800 diluted antibody, however, 1: 400 and 1: 200 diluted solutions provided stronger immunostaining in early stages of islet amyloidogenesis after treating the deparaffinized sections with formic acid.

Methods: Using commercially available rabbit antihuman IAPP antibody, immunocytochemical staining was performed on 18 cases of pancreatic tissues from type 2 diabetic subjects by systematically immunostaining for insulin, glucagon, somatostatin (SRIF) and IAPP compared with controls. Sizes of islets were measured by 1 cm scale, mounted in 10X eye piece.

Conclusions/Interpretation: α cells were major islet cells in majority of diabetic pancreas (83%) and all diabetic islets contained less IAPP-positive cells than controls, indicating that IAPP deficiency in pancreatic islets is responsible for decreased IAPP in blood. In diabetic islets, water-soluble IAPP disappeared in β-cell granules, which transformed to water-insoluble amyloid deposits. Amyloid deposits were not readily immunostained using IAPP 1: 800 diluted antibody but were stronger immunostained for IAPP in early stages of amyloid deposited islets using less diluted solutions after formic acid treatment. In early islet amyloidogenesis, dying β-cell cytoplasm was adjacently located to fine amyloid fibrils, supporting that IAPP in secretary granules from dying β cells served as nidus for islet β-sheet formation.     

Islet amyloid polypeptide in pancreatic islets from type 2 diabetic subjects

Aims/hypothesis: Islet amyloid polypeptide (IAPP) is a chief constituent of amyloid deposits in pancreatic islets, characteristic histopathology for type 2 diabetes. The goal of this study was to analyze islet cell composition in diabetic islets for the process of transforming water-soluble IAPP in β-cells to water-insoluble amyloid deposits by Immunocytochemical staining using different dilutions of anti-IAPP antibody. IAPP in β-cell granules may initiate β-cell necrosis through apoptosis to form interstitial amyloid deposits in type 2 diabetic islets. Results: Control islets revealed twice as much β-cells as α-cells whereas 15 of 18 type 2 diabetic cases (83%) revealed α- cells as major cells in larger islets. Diabetic islets consisted of more larger islets with more σ-cells than β-cells, which contribute to hyperglucagonemia. In control islets, percentage of IAPP-positive cells against β-cells was 40–50% whereas percentage for type 2 diabetic islets was about 25%. Amyloid deposits in diabetic islets were not readily immunostained for IAPP using 1: 800 diluted antibody, however, 1: 400 and 1: 200 diluted solutions provided stronger immunostaining in early stages of islet amyloidogenesis after treating the deparaffinized sections with formic acid. Methods: Using commercially available rabbit antihuman IAPP antibody, immunocytochemical staining was performed on 18 cases of pancreatic tissues from type 2 diabetic subjects by systematically immunostaining for insulin, glucagon, somatostatin (SRIF) and IAPP compared with controls. Sizes of islets were measured by 1 cm scale, mounted in 10X eye piece. Conclusions/Interpretation: α cells were major islet cells in majority of diabetic pancreas (83%) and all diabetic islets contained less IAPP-positive cells than controls, indicating that IAPP deficiency in pancreatic islets is responsible for decreased IAPP in blood. In diabetic islets, water-soluble IAPP disappeared in β-cell granules, which transformed to water-insoluble amyloid deposits. Amyloid deposits were not readily immunostained using IAPP 1: 800 diluted antibody but were stronger immunostained for IAPP in early stages of amyloid deposited islets using less diluted solutions after formic acid treatment. In early islet amyloidogenesis, dying β-cell cytoplasm was adjacently located to fine amyloid fibrils, supporting that IAPP in secretary granules from dying β cells served as nidus for islet β-sheet formation.     

Insulin improves well-being for selected elderly type 2 diabetic subjects

The effects of insulin therapy on patient well-being, treatment satisfaction and mood, and on carer strain were studied in 30 elderly Type 2 diabetic patients (age 73 +/- 7 (SD) yr) in poor glycaemic control on tablet therapy. A comparison group of ten poorly controlled patients who remained on oral agents was also studied. After 4 weeks of insulin treatment, there were significant improvements in mental health, role-emotional, role-physical (all P<0.05) and vitality (P<0.01) domains of the short form health survey (SF-36), and also in the diabetes treatment and satisfaction questionnaire (DTSQ) and geriatric depression scale (both P<0.01) compared to baseline. After 12 weeks, the improvements in mental health, social functioning and vitality (P<0.01 for all domains), and in the DTSQ were sustained. Carer strain was lower at 4 weeks. No changes in outcomes were seen in the comparison group. In selected elderly Type 2 diabetic patients, insulin treatment is associated with significant improvements in well-being, treatment satisfaction and mood, even without significant improvements in glycaemic control and without increase in carer strain. The SF-36 and DTSQ are sensitive to the benefits of the changes in the treatment for these patients.     

Diabetes control in type 2 diabetic subjects treated in primary health care

Aim of the study was to assess control of type 2 diabetes in subjects treated by general practitioners. Study was conducted in one of the primary health care centers in a big city, in which health care was provided for 27 900 inhabitants. Control of diabetes was assessed in 355 of all 936 type 2 diabetic subjects registered in the center. None of them was seen by diabetologist in the preceeding year. Mean age was 65,7 +/- 10,3 lat, diabetes duration 9,2 +/- 7,3 lat, BMI 29,9 +/- 4,9 kg/m2. Normal body weight was found in 15%, overweight in 39%, obesity in 46% of subjects. Hypertension was present in 81%, dyslipidaemia in 62% of patients. Mean HbAlc was 7,2 +/- 1,3%, fasting serum glycaemia 144 +/- 48 mg/dl, total cholesterol 204 +/- 45 mg/dL, LDL - 119 +/- 33 mg/dL, HDL - 51 +/- 13 mg/dl, triglicerides 182 +/- 108 mg/dL. Mean systolic blood pressure was 146 +/- 20 mmHg, diastolic 83 +/- 11 mmHg. Treatment goals recommended by Polish Diabetological Association in 2005 were attained as follows: HbAlc < or = 6,1% - 19,7% of subjects, fasting glycaemia < or =110 mg/dl - 24%, total cholesterol < 175 mg/dl - 26%, LDL < 100 mg/dl - 29%, triglicerides < 150 mg/dl - 46%, cholesterol HDL > 40 mg/dl in men and > 50 mg/dl in women - 65% of subjects. Recommended systolic blood pressure < 130 mmHg was found in 16 %, diastolic blood pressure < 80 mmHg - in 24%, and both values - in 8% of diabetics. In no one subject all recommended treatment goals were met. Conclusions 1. Recommended treatment goals are perceived in unacceptably low number of type 2 diabetic subjects treated by general practitioners. 2. Medical care of type 2 diabetic subjects performed in primary health care is unsatisfactory and should be essentially improved or changed.     

Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: relationship to glucose disposal

The goal of this work was to compare the effects of different antidiabetic therapies on the phenotype of skeletal muscle in type 2 diabetic subjects failing sulfonylurea therapy. Subjects were treated with a thiazolidinedione (troglitazone, TGZ) or a biguanide (metformin, MET) in addition to glyburide for 3 to 4 months. Insulin action was determined with a hyperinsulinemic (300 mU. m(-2). min(-1)) euglycemic (5.0 to 5.5 mmol/L) clamp. Biopsies were obtained from the vastus lateralis muscle for morphological analysis. Despite similar glycemic control, relative increases in the insulin-stimulated glucose disposal rate (GDR) were greater after TGZ treatment (37 +/- 8% increase, P <.05) than after MET (21 +/- 11%, P <.05). Neither treatment had any effect on fiber type composition of the muscle. Capillary density was reduced in diabetic subjects compared to a nondiabetic group (P <.01) and was increased with TGZ treatment (P <.05), while MET was without significant effect. Diabetic muscle also displayed a lower mitochondrial volume density that was unaltered by either treatment. Both TGZ and MET therapy resulted in a reduction in the lipid content of muscle (percent fiber volume as lipid droplets); the relative decrease tended to be greater for TGZ (-33% v -23% for MET). The relative (%) improvement in GDR was correlated with the change in lipid content (r = -0.756, P <.05) after TGZ treatment; no such relationship was observed for MET. From these results we conclude that the higher potency of TGZ to increase capillary density and reduce the lipid content of muscle may contribute to its greater ability to improve glucose disposal in skeletal muscle of type 2 diabetic individuals.