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  • 1
    ISSN: 0009-9120
    Keywords: 2-oxoglutaric acids ; 3-hydroxy-3-methylglutaric ; adipic ; diabetes ; plasma organic acid determination
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0009-9120
    Keywords: 2-oxoglutaric acids ; 3-hydroxy-3-methylglutaric ; adipic ; diabetes ; plasma organic acid determination
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: pancreatogenic diabetes ; pancreatectomy ; glucagon ; alanine ; lactate ; pyruvate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High levels of gluconeogenic precursors have been reported in patients with long-term diabetes secondary to total pancreatectomy. In the present study, blood concentrations of alanine, lactate and pyruvate were measured in six patients undergoing total pancreatectomy and in nine control subjects undergoing major abdominal surgery. To exclude the simple effect of lack of insulin and hyperglycaemia in the development of hyperalaninaemia following total pancreatectomy, three pancreatectomized patients and five control subjects underwent surgical operation while connected to an artificial pancreas. Blood concentration of alanine was constant in the control subjects during surgery (182±20 and 243±31 μmol/l with and without the artificial pancreas, respectively). In pancreatectomized patients basal blood alanine levels were similar to those in control subjects. Blood alanine level rose quickly after removal of the pancreas from 182±24 to 285±15 μmol/l (p〈0.05) in the patients connected to the artificial pancreas, and from 198±17 to 395±47 μmol/l (p〈0.05) in patients undergoing total pancreatectomy without artificial pancreas. These values were higher than those observed in the control subjects at the end of the operation (192±22 and 230±45 μmol/l with and without artificial pancreas, respectively.) Basal and intraoperative blood concentrations of lactate and pyruvate were similar in pancreatectomized patients and control subjects.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Metabolic control ; artificial pancreas ; lactate ; pyruvate ; glycerol ; non-esterified fatty acids ; total ketone bodies ; glucose turnover ; glucose recycling ; glucagon ; growth hormone ; Type 1 diabetes ; subcutaneous insulin therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin infusion system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3±0.7 compared with 5.6±0.3 mmol/l on feedback control and 5.5.±0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94±0.04 on subcutaneous insulin, 0.91±0.04 on feedback control and 0.74±0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600–1800 h) was normal on feedback control (1.41±0.20 versus 1.55±0.18 mg · kg-1 · min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04±0.09 mg · kg-1 · min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; arterial hypertension ; borderline hypertension ; microalbuminuria ; diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arterial hypertension and poor glycaemic control are central to the development of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Recent consensus has established sensitive criteria for their detection and treatment, although the proportion of patients who may benefit is unclear. Between 1988 and 1990, we measured urinary albumin to creatinine concentration ratio (A/C) in 3,636 adult out-patients with IDDM of more than 3 years duration, serum creatinine under 133 Μmol/l and who were not undergoing antihypertensive treatment. A/C indicating microalbuminuria (≥2.38/ 2.96 mg/mmol, male/female) was found in 620 of 3,451 patients without proteinuria, and associated with hypertension (blood pressure ≥140 and/or 90 mm Hg; p=0.0016; rate: 39.6%), independent of diabetes duration (p=0.0082) and male gender (p=0.0350; relative risk=1.16; 95% confidence interval: 1.01–1.32). Hypertension was less common among those with normal A/C (27.5%, p〈0.0001) but was positively related with diabetes duration. Of the 1,015 patients with A/C〉2.0 mg/mmol 529 were reexamined. Glycated haemoglobin levels exceeded 3 SD above the mean of normal in 84.3% of the 198 microalbuminuric patients (AER=20–200 Μg/min), but were comparably poor (79.2%) in normoalbuminuria. Duration of diabetes was inversely related to glycated haemoglobin only in microalbuminuria (0.05〈p〈0.1). Intervention to lower blood pressure remains mainly restricted to those patients with long-term diabetes and slower development of kidney disease. Near-normalisation of glycaemia remains the priority for the majority of patients with microalbuminuria.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords NIDDM ; renal structure ; microalbuminuria ; glomerular filtration rate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria predicts overt nephropathy in non-insulin-dependent diabetic (NIDDM) patients; however, the structural basis for this functional abnormality is unknown. In this study we evaluated renal structure and function in a cohort of 34 unselected microalbuminuric NIDDM patients (26 male/8 female, age: 58 ± 7 years, known diabetes duration: 11 ± 6 years, HbA1 c: 8.5 ± 1.6 %). Systemic hypertension was present in all but 3. Glomerular filtration rate (GFR) was 101 ± 27 ml · min–1· 1.73 m–2 and albumin excretion rate (AER) 44 (20–199) μg/min. Light microscopic slides were categorized as: C I) normal or near normal renal structure; C II) changes “typical” of diabetic nephropathology in insulin-dependent diabetes (IDDM) (glomerular, tubulo-interstitial and arteriolar changes occurring in parallel); C III) “atypical” patterns of injury, with absent or only mild diabetic glomerular changes associated with disproportionately severe renal structural changes including: important tubulo-interstitial with or without arteriolar hyalinosis with or without global glomerular sclerosis. Ten patients (29.4 %) were classified as C I, 10 as C II (29.4 %) and 14 as C III (41.2 %); none of these patients had any definable non-diabetic renal disease. GFR, AER and blood pressure were similar in the three groups, while HbA1 c was higher in C II and C III than in C I patients. Diabetic retinopathy was present in all C II patients (background in 50 % and proliferative in 50 %). None of the patients in C I and C III had proliferative retinopathy, while background retinopathy was observed in 50 % of C I and 57 % of C III patients. In summary, microalbuminuric NIDDM patients are structurally heterogeneous with less than one third having “typical” diabetic nephropathology. The presence of both “typical” and “atypical” patterns of renal pathology was associated with worse metabolic control, suggesting that hyperglycaemia may cause different patterns of renal injury in older NIDDM compared to younger IDDM patients. [Diabetologia (1996) 39: 1569–1576]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Metalloproteinases ; MMP2 ; TIMP2 ; non-insulin-dependent diabetes mellitus ; diabetic nephropathy ; microalbuminuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regulation of mesangial matrix deposition is a dynamic phenomenon involving synthetic and degradative processes. The latter involve a number of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP). Experimental studies suggest that mesangial matrix degradation is inhibited in diabetic nephropathy, and that this phenomenon has a pathogenic role. The expression of genes for MMP2 and TIMP2 in human diabetic nephropathy was investigated. Reverse transcription polymerase chain reaction was carried out in microdissected glomeruli and tubulo-interstitium obtained from kidney biopsies. We studied 16 NIDDM patients, 5 patients with glomerulonephritis or chronic kidney transplant rejection, and 5 normal control subjects. Albumin excretion rate and renal histology for NIDDM patients were available. Contrary to TIMP2 which was expressed both in tubulo-interstitium and glomeruli in almost all renal biopsies, MMP2 gene down-regulation was observed in glomeruli from all NIDDM patients, irrespective of the albumin excretion rate, and of renal histology. In contrast, this gene was expressed in biopsies from other subjects (χ2 = 20.6; p = 0.000). In conclusion, this study demonstrates that: 1) in glomeruli of NIDDM patients the MMP2 gene is down-regulated; 2) in biopsies of NIDDM patients the MMP2/TIMP2 pattern is peculiar for NIDDM; 3) the MMP2 gene down-regulation is observed in all NIDDM patients, irrespective of the level of albuminuria and of renal histology. MMP2 gene down-regulation seems to be a molecular epiphenomenon of diabetes, rather than a marker of diabetic nephropathy. [Diabetologia (1997) 40: 1449–1454]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Diabetic nephropathy ; erythrocyte sodium-lithium countertransport activity ; hypertension.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pathogenetic mechanisms other than the quality of metabolic control may play a role in the development of diabetic nephropathy. Some cross-sectional studies have shown that elevated erythrocyte sodium-lithium countertransport (Na + /Li + CT) activity may be linked to incipient or overt nephropathy in insulin-dependent diabetic (IDDM) patients. The aim of the present work was to ascertain if high erythrocyte Na + /Li + CT activity anticipates the development of microalbuminuria in IDDM patients. Evaluation of this cation transport system was carried out in 159 normotensive, normoalbuminuric IDDM patients, who were divided into two groups: those with values above (Group A) and those with values below (Group B) the median level in the overall population (300 μmol/erythrocytes × h). A total of 79 patients in Group A and 80 in Group B underwent periodic examinations over a similar time period (5.2 years, range 3.3–7.4 years and 5.4 years, range 3.4–7.5 years, respectively). Median sodium-lithium countertransport activity was stable when evaluated after 2 and 4 years of follow-up. Only seven patients were excluded from the protocol because changes in their sodium-lithium countertransport activity placed them on the other side of the median value with respect to their baseline measurement. Thus, 152 patients completed the study (76 in Group A and 76 in Group B). Of the 76 patients in Group A, 17 developed persistent microalbuminuria (22.3 %). The number of patients in Group B showing persistent microalbuminuria was significantly lower (4 of 76; 5.2 %; p 〈 0.01). The sensitivity of erythrocyte Na + /Li + CT in predicting the development of microalbuminuria was 85 % and its specificity was 55 %. Seven patients of Group A and five of Group B developed arterial hypertension. Subjects in Group A had significantly higher mean HbA1 c values of twice yearly measurements than those in Group B (9.6 ± 1.7 vs 8.3 ± 1.7 %, p 〈 0.002, mean ± SD) despite similar daily insulin requirements. Systolic and diastolic blood pressure levels were also evaluated every 6 months and were significantly higher in the Group A than in the Group B patients, although on average within the normal range. The odds ratio for developing persistent microalbuminuria in IDDM with elevated baseline erythrocyte Na + /Li + CT activity after adjustment for gender and baseline albumin excretion rate, and mean 6 monthly plasma creatinine, HbA1 c and systolic and diastolic blood pressure levels was 4.2 (95 % confidence intervals 2.0–11.1). It was also found that the percentage of offspring having both parents with Na + /Li + CT activity above the median value was significantly higher in Group A than in Group B (Group A vs Group B: 35 vs 19 %; p 〈 0.01). On the contrary the percentage of offspring whose erythrocyte Na + /Li + CT was lower in both parents was lower in Group A than in Group B: 10 vs 38 %, p 〈 0.01). Parents of Group A offspring had arterial hypertension more frequently than those of Group B. These results indicate that erythrocyte Na + /Li + CT activity is a useful diagnostic tool in identifying normotensive, normoalbuminuric patients who may be predisposed to develop persistent microalbuminuria. This disorder in the cation transport system is associated with poor metabolic control, higher blood pressure, and male sex; it also appears to be, at least partly, genetically transmitted. [Diabetologia (1997) 40: 654–661]
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; micro-macroalbuminuria ; familial clustering ; sib pair analysis ; diabetic retinopathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Proteinuria and nephropathy have been found to cluster in families of non-insulin-dependent diabetic (NIDDM) Pima Indian, and in Caucasian insulin-dependent diabetic (IDDM) patients. No information is at present available for Caucasian NIDDM patients. The aim of the present study was to determine whether micro-macroalbuminuria (AER + ) is associated with albumin excretion rate abnormalities in diabetic and non-diabetic siblings of probands with NIDDM and AER + . We identified 169 Caucasian families with one NIDDM proband (the patient with longest known NIDDM duration) (101 families with only NIDDM siblings, 33 families with both NIDDM and non-NIDDM siblings and 35 families with only non-NIDDM siblings). Of the probands 56 had AER + [Prob-NIDDM-(AER + )], 78 had AER– [Prob-NIDDM-(AER–)], 74 siblings of Prob-NIDDM-(AER + ), and 113 siblings of Prob-NIDDM-(AER–) also had NIDDM. Data on albuminuria and retinopathy from multiple sibling pairs when the size of the sibship was more than two was adjusted according to a weighting factor. The odds ratio for AER + , in siblings of Prob-NIDDM-(AER + ) adjusted for age, hypertension, glycated haemoglobin A1 c and other confounding variables was 3.94 (95 % confidence intervals: 1.93–9.01) as compared to siblings of Prob-NIDDM-(AER–). The 74 siblings of Prob-NIDDM-(AER + ) had higher prevalence of proliferative retinopathy than siblings of Prob-NIDDM-(AER–) (14 vs 2 %; p 〈 0.01). We also identified 66 non-diabetic siblings of 41 NIDDM probands with AER + and 36 non-diabetic siblings of 27 NIDDM probands with AER–. Albumin excretion was two times higher, although still within the normal range, in the non-diabetic siblings of Prob-NIDDM-(AER + ) than in siblings of Prob-NIDDM-(AER–) [median = 13.5 (range 0.5–148) vs 6.6 (range 1–17) μg/min (p 〈 0.05)]. In conclusion higher rates of albumin excretion aggregate in Caucasian families with NIDDM. Proliferative retinopathy is more frequently observed in families showing a clustering of AER + and NIDDM. These findings suggest that familial factors play a role in the pathogenesis of renal and retinal complications in NIDDM. [Diabetologia (1997) 40: 816–823]
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Artificial endocrine pancreas ; glucose clamping ; hyperglycaemia ; insulin-dependent diabetes ; blood glucose ; ketone bodies ; alanine ; lactate ; pyruvate ; ketogenesis ; insulin ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic and hormonal effects of stable hyperglycaemia (10–12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5–6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lactate, pyruvate, total ketone bodies, glycerol and plasma nonesterified fatty acids were similar during the period of stable glycaemia at the two glucose levels. In contrast mean blood alanine was markedly elevated during hyperglycaemic clamping (0.384 ± 0.008 vs 0.298 ± 0.021 mmol/l) and 3-hydroxybutyrate was slightly decreased (0.068 ± 0.007 vs 0.084 ± 0.008 mmol/l). Plasma glucagon levels were raised during hyperglycaemic clamping and growth hormone slightly decreased. There was a close positive correlation between mean blood alanine and mean blood glucose (r = 0.79, p 〈 0.01), and a negative correlation of alanine with the amount of insulin infused (r =-0.72, p 〈 0.01). It is suggested that the raised alanine results from increased peripheral glucose utilisation. In general a short period of stable hyperglycaemia is not associated with a worsening of metabolic abnormalities in insulin-dependent diabetic subjects.
    Type of Medium: Electronic Resource
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