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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; insulin resistance ; euglycaemic hyperinsulinaemic clamp ; intensified insulin therapy ; HbA1c ; near-normoglycaemia ; continuous insulin infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To determine the impact of both short- and longterm “near-normoglycaemia” on insulin resistance in Type 1 (insulin-dependent) diabetes hepatic glucose production (mg · kg−1 · min−1) and peripheral glucose utilisation (“M-value”, mg · kg−1 · min−1) were estimated during an euglycaemic hyperinsulinaemic clamp (10 mU · kg · min) in patients with either good (HbA1c〈5.8%, groups A and B) or poor (HbA1c〉7.5%, groups C and D) long-term metabolic control (time 〉 12 months) and in healthy subjects (HbA1c: 5.08±0.20%; n=8). To this end blood glucose was stabilized at 6.7 mmol/l by overnight (t=12 h) i.v. regular insulin in groups (n=8 each) A (HbA1c: 5.49±0.46%) and C (HbA1c: 8.83±1.20%),while groups B (HbA1c:5.55±0.19%) andD (HbA1c: 8.51±1.09%) were kept overnight on long-acting insulin without feed-back control of blood glucose before euglycaemic clamping. Thereby, pre-equilibration of blood glucose at 6.7 mmol/l was shown to normalize basal hepatic glucose production (A: 2.27±0.48; C 2.50±0.57 mg · kg−1 · min−1) despite different HbA1c values, whereas basal hepatic glucose production stayed elevated in groups B (3.09±0.38 mg · kg−1 · min−1) and D (3.21±0.58 mg · kg−1 · min−1) with poor actual glycaemia (B: 10.9±4.6; D: 12.1±4.6 mmol/l). To restitute peripheral glucose utilisation close to normal (healthy subjects: 13.99±2.13; A: 12.12±2.67; B: 8.72±3.0; C: 10.27±1.69; D: 7.10±2.31 mg · kg−1 · min−1; healthy subjects vs A: NS; healthy subjects vs B, C, D: p〈0.05) both long-term (HbA1c〈5.8%) and acute nearnormoglycaemia by 12-h i. v. insulin pre-treatment were required (group A). We conclude that good long-term glucose control per se is unable to normalize hepatic and peripheral glucose metabolism in Type 1 diabetic patients unless actual near-normoglycaemia is provided consistently, e.g. by i.v. overnight infusion of regular insulin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1438-2199
    Keywords: Amino acids ; Western blot ; Immunoglobulin G ; Cross linking-polymerization ; Diabetes mellitus ; 3-Deoxyglucosone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is well known that increased cross linking of proteins due to nonenzymatic glycosylation occurs in diabetic animals and humans leading to accumulation of proteins (e.g. collagen). This in turn is strongly associated with diabetic long term complications. We developed a noninvasive method for studying in vivo cross linking and its pharmacological inhibition by L-arginine in a blind placebo controlled study with crossing over of two treatment periods of three months each. Glycemic control was assessed by determining blood glucose, HbA1c, fructosamine, and total glycosylated hemoglobin. The patients were randomly assigned to two treatment groups A (n = 14) and B (n = 16). 20 healthy volunteers served as controls. Treatment consisted of two daily dosages of 1 g L-arginine free base. Cross linking of a human serum protein (IgG) was assessed by SDS polyacrylamide gel electrophoresis and subsequent Western blotting. Diabetic patients showed a statistically increased number of cross links compared to normal controls (Group A: 3.6 vs 2.0 bands, group B: 3.8 vs 2.0 bands). L-arginine led to a significant reduction of cross links in both treatment groups (Group A: 3.6 to 2.1 bands, group B: 3.8 to 2.5 bands). The described noninvasive method for assessing in vivo cross linking requires onlyµl amounts of serum and could serve to monitor protein cross linking in patients with diabetes mellitus.
    Type of Medium: Electronic Resource
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