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Biomedical subjects

A Flyvbjerg

Publications and source records attributed to A Flyvbjerg.

At least 19 recordsLinked to original sources
PubMed2006

Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear. SUBJECTS AND METHODS: Combining euglycaemic-hyperinsulinaemic clamp studies with indirect calorimetry and skeletal muscle biopsies, we examined the relationship between plasma adiponectin and parameters of whole-body glucose and lipid metabolism, and muscle glycogen synthase (GS) activity in 51 Caucasians (ten lean, 21 obese and 20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes. Plasma adiponectin was positively associated with insulin-stimulated glucose disposal (r = 0.48), glucose oxidation (r = 0.54), respiratory quotient (r = 0.58) and non-oxidative glucose metabolism (r = 0.38), and negatively associated with lipid oxidation during insulin stimulation (r = -0.60) after adjustment for body fat (all p < 0.01). Most notably, we found a positive association between plasma adiponectin and insulin stimulation of GS activity in skeletal muscle (r = 0.44, p < 0.01). CONCLUSIONS/INTERPRETATION: Our results indicate that plasma adiponectin may enhance insulin sensitivity by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes.

Adiponectin↗
PubMed2006

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure.

OBJECTIVE: It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. DESIGN: We studied eight nondiabetic patients with CHF (ejection fraction 30 +/- 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. RESULTS: Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg(-1) min(-1)): 1.25 +/- 0.09 (patients) vs. 1.55 +/- 0.09 (controls), P < 0.01] and muscle glucose uptake [a - v diff(glucose) (micromol L(-1)): -10 +/- 25 (patients) vs. 70 +/- 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L(-1)): 0.72 +/- 0.05 (patients) vs. 0.48 +/- 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a - v diff(FFA) (mmol L(-1)): 0.12 +/- 0.02 (patients) vs. 0.05 +/- 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (micromol kg(-1) h(-1)): 36.4 +/- 1.5 (patients) vs. 29.6 +/- 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. CONCLUSIONS: In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention.

Aged↗
PubMed2006

Growth hormone is a stimulating but not an essential factor in healing of colon. A study in GH-deficient dwarf rats.

BACKGROUND: Growth hormone (GH) has been implicated as an important factor in the healing and previous studies showed significant strength acceleration of experimental intestinal anastomoses. AIM: To study the healing of experimental colonic anastomoses in GH-deficient rats and to study the potential physiological effects of GH-substitution on healing parameters. CONCLUSION: Exogenous rhGH treatment started 7 days prior to surgery and continued until day 4 postoperatively accelerates the strength development of the experimental colonic anastomoses in dwarf rats indicating a potent role of growth hormone in colonic healing. However, GH is not essential in the healing process, since anastomotic healing in GH-deficient dwarf rats is like rats with normal pituitary function.

Anastomosis, Surgical↗
PubMed2006

Zinc ions in the endocrine and exocrine pancreas of zinc deficient rats.

OBJECTIVE: Zinc deficiency is a problem world-wide. Zinc and insulin are intimately related, and a reduced zinc intake may affect glucose metabolism. The present study investigates how subclinical zinc deficiency in rats affects glucose metabolism and zinc distribution in the pancreas. METHODS: Glucose metabolism was evaluated by blood-glucose, serum insulin, homeostasis model assessment (HOMA), and intraperitoneal glucose tolerance tests. Immersion zinc-sulphide autometallography (iZnSAMG) was used to describe zinc ion distribution. RESULTS: After 4 weeks on a zinc deficient diet (<10 ppm), the zinc deficient rats had a slightly impaired glucose metabolism characterized by significantly increased blood-glucose levels. No differences in serum insulin, insulin resistance, beta-cell function were observed. The zinc deficient rats had significantly decreased serum zinc without any clinical signs of zinc deficiency. Zinc ion staining intensity of the islets of Langerhans was unaffected by the zinc deficiency. In contrast, the acinar cells in the exocrine pancreas appeared depleted of iZnSAMG grains in the zinc deficient rats when compared with their controls. Though statistically non-significant, a reduction in total zinc of the pancreas was found. CONCLUSIONS: The present findings suggest that the endocrine pancreas is able to compensate for the subclinical zinc deficiency as it maintains an adequate zinc ion level in the secretory vesicles for insulin storage. The exocrine pancreas lacks this ability; it exhibits decreased levels of zinc ion staining as a consequence of 4 weeks of reduced zinc intake.

Animal Feed↗
PubMed2005

The effect of intrauterine environment and low glomerular number on the histological changes in diabetic glomerulosclerosis.

AIMS/HYPOTHESIS: We tested the hypothesis that diabetic glomerulosclerosis would develop more rapidly in animals with fewer glomeruli. METHODS: We studied the female offspring of Wistar rats that had been fed a low-protein diet (LPD) containing 6% protein or a normal-protein diet (NPD) containing 18% protein during pregnancy. Streptozotocin diabetes was induced at 12 weeks and animals were killed at 40 weeks. RESULTS: Non-diabetic LPD offspring were of lower birthweight than the NPD offspring (5.19+/-0.64 vs 6.45+/-0.67 g, p<0.001) and had fewer glomeruli (27,402+/-3,137 vs 34,203+/-6,471, p<0.05). Glomerular volume correlated inversely with glomerular number (r=-0.64, p=0.035), but total glomerular filtration surface area was reduced in the LPD animals (4,770+/-541 vs 5,779+/-1,302 mm(2), p=0.05). Other renal structural and functional parameters were similar. In LPD and NPD diabetic animals, glomerular volume and basement membrane width were significantly increased compared to their respective controls. Podocyte density was lowest in the LPD diabetic animals (not significant), and the area covered by each podocyte was greater in the LPD diabetic group (2.40+/-0.693 x10(-3) mm(2)) than in the LPD control group (1.68+/-0.374 x10(-3) mm(2), p<0.001) and in the NPD diabetic animals (1.71+/-0.291 x 10(-3) mm(2), p<0.05). There was no difference in any other structural or functional parameter between the LPD and NPD diabetic animals. CONCLUSIONS/INTERPRETATION: A decrease in glomerular number was not deleterious to renal structure and function over 40 weeks in this animal model. Further work in models with progressive renal impairment and hypertension is necessary to clarify the impact of glomerular number on the development of renal disease.

Animals↗
PubMed2005

Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications.

AIMS/HYPOTHESIS: Low serum adiponectin (ADPN) has been associated with increased risk of cardiovascular disease (CVD) and retinopathy in patients with type 2 diabetes mellitus. In type 1 diabetic patients, the relationship between ADPN and the presence of vascular complications is largely unknown. METHODS: We investigated the relationship between serum ADPN and the presence of retinopathy, nephropathy and CVD in patients with type 1 diabetes, divided into matched groups with normoalbuminuria and no retinopathy (n=67), simplex retinopathy (n=106) or proliferative retinopathy (n=19), and nephropathy with simplex (n=62) or proliferative retinopathy (n=137). Healthy control subjects (n=25) were included. RESULTS: Serum ADPN was increased in subjects with type 1 diabetes compared with control subjects (p<0.0001). Further, serum ADPN was higher in patients with than in those without nephropathy (p<0.0001). It was also higher in normoalbuminuric patients with than in those without proliferative retinopathy (p<0.0001). These differences remained significant after adjustment for known risk factors (p<0.03). CVD was also associated with elevated ADPN levels (p<0.05), but this difference became insignificant after risk factor adjustment. The most important predictor of serum ADPN was sex (r2=19%) in normoalbuminuric patients and GFR in patients with nephropathy (r2=18%). CONCLUSION/INTERPRETATION: Patients with type 1 diabetes and microvascular complications have higher serum levels of ADPN than patients without complications. It remains to be clarified whether elevated levels of ADPN are pathogenically related to the development of microvascular complications or represent a beneficial counter-regulatory response.

Aged↗
PubMed2005

The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). Recent studies have demonstrated significant changes in the IGF system in IBD patients. The aim of the present study was to investigate correlations between the IGF system and markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99 IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)). Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were examined in CD and UC patients in remission and relapse. The patients were clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and Activity Index (AI) for UC patients. RESULTS: In the UC group we found correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p < 0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p < 0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = -0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p < 0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p < 0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF-II is correlated to IL-6 in IBD patients. This may suggest a correlation between inflammation and the IGF system with involvement in muscle and bone catabolism in IBD.

Adult↗
PubMed2005

Effects of pure ethanol and alcopops on glucose, insulin, and the insulin-like growth factor system in healthy subjects.

INTRODUCTION: Alcohol induces disturbances in insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) levels. The aim of the present study was to compare pure ethanol and alcopop effects on total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, insulin and plasma glucose levels in healthy subjects. METHODS: Five males and seven females (21-51 years) consumed pure ethanol and alcopops with identical alcohol content in a cross-over design after 6h fasting. Blood samples were obtained for determination of serum ethanol and plasma glucose at 0, 30, 60, 90, 120 and 180 min. Serum total and free IGF-I, IGFBP-1, IGF-I:IGFBP-1 complex, and insulin were measured at 0, 60 and 180 min. RESULTS: Area under the curve for serum ethanol concentration was significantly less following alcopop compared to pure ethanol (1124+/-201 vs. 1691+/-359 mmol/Lh, P<0.01). Serum insulin and glucose levels were unchanged by ethanol while alcopop intake was followed by a transient increase in glucose and insulin levels (P<0.05). Pure ethanol and alcopop reduced free IGF-I levels by the end of the study period (P=0.05). IGFBP-1 and the IGF-I:IGFBP-1 complex increased following ethanol intake (P<0.05) while only a small transient IGFBP-1 increase was observed following alcopop intake. No change in total IGF-I was observed. CONCLUSION: Both drinks resulted in reduced free IGF-I levels, however, only pure ethanol increased IGFBP-1 and the IGF-I:IGFBP-1 complex. Alcopop intake was associated with a transient increase in IGFBP-1 and unchanged IGF-I:IGFBP-1 complex levels probably due to marked changes in insulin and glucose levels.

Adult↗
PubMed2005

The effect of submaximal exercise on immuno- and bioassayable IGF-I activity in patients with GH-deficiency and healthy subjects.

OBJECTIVE: Growth hormone (GH) increases during exercise, but the response of the insulin-like growth factor (IGF) system has not been as definitive. Therefore, we investigated the effect of the exercise-induced GH response on the circulating IGF-system in GH-deficient (GHD) and intact adults. DESIGN: Eight GHD adults were studied on 2 occasions, with (+GH) and without (-GH) GH administered (0.4 IU) during exercise (45 min of cycle ergometer exercise at the lactate threshold). Eight age-matched controls were only studied on one occasion. Blood samples were drawn at baseline, during and post-exercise. IGFBP-3 proteolysis was measured by an in vitro proteolytic activity assay, IGF-I bioactivity by novel IGF-I kinase receptor activation assay (KIRA) and other hormones by immunoassay. RESULTS: GH administration to GHD adults resulted in a serum GH peak similar to the exercise-stimulated GH response in GH intact controls, but exercise had only a small impact on the IGF system. IGF-I concentration was lower in controls but was only significantly lower than the +GH day. Neither IGF-I nor -II levels changed over time. IGFBP-1 demonstrated a time effect (P<0.01) in all groups, and a time x group interaction (P<0.01) with a rise at 75 min post-exercise, which was greater in the GHD subjects than controls. IGFBP-2 and -3 increased significantly (P<0.01) over time in the GHD subjects, but not in the controls. No change in IGFBP-3 proteolysis or IGF-I bioactivity was found during exercise or recovery in either group. CONCLUSION: Submaximal exercise induced minor changes in IGFBP-1, -2 and -3, without affecting IGFBP-3 proteolysis and IGF-I bioavailability. Thus the metabolic status during submaximal exercise does not require a change in plasma IGF-I bioavailability. Administration of GH to GHD adults does not result in changes in proteolysis or bioavailability.

Adult↗
PubMed2005

Intrarenal blood oxygenation and renal function measured by magnetic resonance imaging during long-term cyclosporine treatment.

Treatment with cyclosporine (CsA) markedly affects the renin-angiotensin-aldosterone system in parallel with an increase in the net tubular reabsorption or a decrease in secretion. Since tubular reabsorption is closely linked to medullary oxygen consumption, the aim of the present study was to investigate the intrarenal oxygenation and renal function in response to CsA. Six mini Göttingen pigs were treated with CsA (10 mg/kg/d) for 6 months. The intrarenal oxygenation was indirectly measured as R2* obtained with a multiecho gradient-echo magnetic resonance imaging (MRI) sequence. Single-kidney renal blood flow (skRBF) was measured by a velocity-sensitive gradient-echo MRI sequence. Relative single-kidney glomerular filtration rate (rskGFR) was derived from the MRI time-activity curve in response to an intravenous bolus of Gd-DTPA (0.05 mmol/kg). The present study showed that administration of CsA increased the medullary R2* (23.1 Hz vs 19.0 Hz, P = .002), whereas R2* was slightly increased in the renal cortex (13.3 Hz vs 12.3 Hz, P = .012). In parallel, rskGFR increased significantly (47.2 mL/min vs 19.8 mL/min, P = .005) but skRBF was unchanged (197.6 mL/min vs 202.5 mL/min, P > .05). The increased R2* in the renal medulla indicated that CsA augments the tubular reabsorption of water, leading to increased oxygen consumption. The supply of oxygen to the kidney was, however, maintained during treatment with CsA as suggested by an unchanged renal blood flow. The increased tubular reabsorption was compensated for by an elevated glomerular filtration rate.

Animals↗
PubMed2005

Inhibition of vascular endothelial growth factor (VEGF) does not affect early renal changes in a rat model of lean type 2 diabetes.

Type 2 diabetes is the most frequent cause of end-stage renal failure in many Western countries. Approximately 10-15 % of all type 2 diabetics are lean. Various growth factors and cytokines have been implicated in the pathophysiology of diabetic kidney disease, including vascular endothelial growth factor (VEGF). To elucidate a role for VEGF in the renal changes associated with type 2 diabetes, we examined the effect of a VEGF-antibody (ab) on early renal changes in the Goto-Kakizaki (GK) rat, a lean type 2 diabetes model. GK-rats were treated for 6 weeks with the VEGF-ab or with an isotype-matched irrelevant IgG. Wistar rats were used as non-diabetic controls. Placebo-treated GK-rats showed a pronounced increase in glomerular volume and urinary albumin excretion (UAE) and no change in the renal expression of endothelial nitric oxide synthase (eNOS) compared to placebo-treated non-diabetic controls. Kidney weight and creatinine clearance were no different between the groups. VEGF-ab treatment had no effect on glomerular volume, UAE, eNOS expression, body weight, blood glucose levels or food intake, but lowered serum insulin levels in non-diabetic and diabetic animals. We conclude that VEGF inhibition has minimal effects on early renal changes in GK-rats.

Albuminuria↗
PubMed2005

Zinc fluxes during acute and chronic exposure of INS-1E cells to increasing glucose levels.

Zinc in beta-cell secretory vesicles is essential for insulin hexamerization, and tight vesicular zinc regulation is mandatory. Little is known about zinc ion fluxes across the secretory vesicle membrane and the influence of changes in the extracellular environment on vesicular zinc. Our study aim was to investigate the effect of acute and chronic exposure to various glucose concentrations on zinc in secretory vesicles, the relation between zinc and insulin, and the presence of two zinc transporters, ZnT1 and ZnT4, in INS-1E cells. Zinc ions were demonstrated and semi-quantified using zinc-sulfide autometallography. Insulin content and secreted insulin were measured. Measurements were made on INS-1E cells after exposure to 2.0, 6.6, 16.7, and 24.6 mmol/l glucose for 1, 24, and 96 hours. 1h: Increasing glucose resulted in no changes in intravesicular zinc ions at 2, and 24.6 mmol/l glucose, but a slight increase at 16.7 mmol/l glucose. 24 and 96 h: Increasing glucose led to decreased vesicular zinc ion content accompanied by a decrease in insulin content. ZnT1 and ZnT4 were present in the cytoplasm. Our results demonstrate that intra-vesicular zinc ions respond to changes in the extra-cellolar glucose concentration, especially during chronic high glucose concentrations, where the content of vesicular zinc ions decreases.

Animals↗
PubMed2005

AGE-RAGE and AGE Cross-link interaction: important players in the pathogenesis of diabetic kidney disease.

At present, diabetic kidney disease affects about 15 - 25% of all type 1 diabetic patients and 20 - 40% of all patients with type 2 diabetes. The mechanisms underlying the development of diabetic kidney disease are extremely complex and not yet fully understood. Among the many potential pathogenic mechanisms responsible for the progression in diabetic kidney disease, the involvement of metabolic factors beyond blood glucose (such as advanced glycation end products (AGEs)) has been suggested. This review will present the emerging evidence in support of a significant role of AGE formation in the development of diabetic kidney disease. AGEs mediate their effects through two main pathways - through a receptor-independent AGE cross-link formation pathway and through a receptor-dependent pathway where AGEs bind to specific cell surface associated receptors, the receptor for AGE (RAGE) being the most well-characterised so far. First, we will describe the AGE-RAGE system, including its localisation in the normal kidney, and then move on to discuss in vitro and in vivo studies (that is, experimental and clinical data) in support of a pathogenic role of AGE-RAGE and AGE cross-link interaction in the development of diabetic kidney disease. Finally, the effects of known and potential inhibitors of AGE-RAGE and AGE cross-link systems in diabetic kidney disease will be examined.

Animals↗
PubMed2005

Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients.

AIM: To study the effects of short-term poor glycaemic control on vascular function in Type 1 diabetic patients. METHODS: Ten Type 1 diabetic patients, with diabetes duration of less than 10 years and normal urinary albumin excretion and ophthalmoscopy, were studied. All patients were examined after 48 h of good vs. poor glycaemic control within a 3-week period. Blood glucose was measured seven times daily for 2 days before each examination. External ultrasound was used to measure the dilatory response of the brachial artery to post-ischaemic increased blood flow (endothelium-dependent dilation) and to nitroglycerin (endothelium-independent dilation). Plasma concentration of von Willebrand factor antigen, adhesion molecules, vascular endothelial growth factor, homocystein and cholesterol were also measured. RESULTS: The median blood glucose levels in the 48 h before the examinations were [median (range), good vs. poor control]: 6.3 (5.0-7.6) vs. 15.9 (11.3-17.8) (mmol/l). The flow-associated vasodilation (% of baseline) was reduced during poor control: 102.7 (94.7-110.8) vs. 104.0 (99.6-118.5) (P < 0.05) as were the nitroglycerin-induced dilation (% of baseline): 114.5 (103.3-127.9) vs. 120.2 (106.8-148.0) (P < 0.05). P-von Willebrand factor antigen was high during poor control (kIU/l): 1.14 (0.73-1.84) vs. 0.86 (0.72-1.39) (P < 0.05) and so was P-vascular endothelial growth factor (ng/l): 288 (133-773) vs. 254 (90-383) (P < 0.05). CONCLUSIONS: Short-term (48 h) hyperglycaemia in Type 1 diabetic patients may disturb vascular function, possibly mediated through smooth muscle cell dysfunction as well as endothelial dysfunction. We suggest that prolonged and repeated episodes of hyperglycaemia could possibly lead to permanent vascular dysfunction and thereby development and progression of vascular complications in diabetes.

Adult↗
PubMed2005

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

Blood Flow Velocity↗
PubMed2004

Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy.

AIMS/HYPOTHESIS: Diabetic nephropathy is associated with insulin resistance, and low-grade inflammation and activation of the complement system may contribute to this cascade. Mannan-binding lectin (MBL) activates the complement system, and elevated MBL concentrations have been observed in normoalbuminuric type 1 diabetic patients. The aim of this study was to assess whether MBL is associated with diabetic nephropathy in type 1 diabetes, and whether there is an association between MBL and low-grade inflammatory markers or insulin resistance. METHODS: A total of 191 type 1 diabetic patients from the Finnish Diabetic Nephropathy Study were divided into three groups based upon their AER. Patients with normal AER (n=67) did not take antihypertensive medication, while patients with microalbuminuria (n=62) or macroalbuminuria (n=62) were all treated with an ACE inhibitor. As a measure of insulin sensitivity we used estimated glucose disposal rate. MBL was measured by an immunofluorometric assay, C-reactive protein by a radioimmunoassay and IL-6 by high-sensitivity enzyme immunoassay. RESULTS: Patients with normal AER (median [interquartile range]: 1,154 microg/l [180-2,202 microg/l]) had lower levels of MBL than patients with microalbuminuria (1,713 microg/l [724-2,760 microg/l]; p=0.029) or macroalbuminuria (1,648 microg/l [568-3,394 microg/l]; p=0.019). There was a significant correlation between MBL and estimated glucose disposal rate, but not between MBL and C-reactive protein or IL-6 levels in univariate analysis. However, in a multiple regression analysis, HbA1c was the single variable independently associated with MBL (beta+/-SEM: 0.26+/-0.08; p=0.003). CONCLUSIONS/INTERPRETATION: MBL concentrations are increased in type 1 diabetic patients with diabetic nephropathy. MBL was not associated with low-grade inflammatory markers.

Adult↗
PubMed2004

Ischaemic preconditioning does not protect the heart in obese and lean animal models of type 2 diabetes.

AIMS/HYPOTHESIS: The prevalence of type 2 diabetes mellitus is increasing worldwide with obese diabetic patients constituting the majority of this population. Type 2 diabetes is associated with increased morbidity and mortality after acute myocardial infarction. Previous experimental studies of ischaemia-reperfusion tolerance in diabetes have only been performed in animal models of type 1 diabetes mellitus, yielding conflicting data. The aim of the present study was to characterise and compare the tolerance to ischaemia and effects of ischaemic preconditioning (IPC) in hearts from obese Zucker diabetic fatty (ZDF) and lean Goto-Kakizaki (GK) type 2 diabetic rats, using non-obese Zucker and Wistar rats as respective controls. METHODS: The two rat strains were divided into 8 groups. The ZDF study (n=47) consisted of: Control -IPC, Control +IPC, ZDF -IPC and ZDF +IPC. The GK study (n=38) consisted of: Control -IPC, Control +IPC, GK -IPC and GK +IPC. Hearts, which were studied in a Langendorff preparation perfused with Krebs-Henseleit buffer, were subjected or not to IPC (+IPC, -IPC) before 50 minutes of regional ischaemia and 120 minutes reperfusion. RESULTS: Ischaemic reperfusion injury was smaller in obese (p<0.05) and lean (p<0.05) type 2 diabetic animals than in their respective control animals. IPC reduced ischaemic reperfusion injury during reperfusion in non-diabetic control rats (p<0.01), but failed to protect hearts from both diabetic animal models. Post-ischaemic haemodynamic recovery was impaired in the ZDF rats compared to both control and GK rats (p<0.05). CONCLUSIONS/INTERPRETATION: Ischaemic preconditioning does not protect hearts from obese or lean type 2 diabetic animals. However, the susceptibility of the type 2 diabetic myocardium to ischaemic damage is lower than in non-diabetic hearts. The method described here could be used as a tool to study the pathogenesis of increased cardiovascular morbidity and mortality in type 2 diabetes.

Animals↗