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  • 1
    ISSN: 1438-2199
    Keywords: Collagen cross links ; Glucose mediated cross links ; Diabetes mellitus ; L-arginine ; Long term complications ; Hexosyl lysines ; Glycosylated lysines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long term complications of diabetes mellitus are largely due to chemical, structural and mechanical changes of connective tissue proteins involving glucose mediated collagen cross links (GMCC). To date there are only experimental therapeutic approaches for preventing long term complications of diabetes mellitus using the toxic substance aminoguanidine.L-arginine, a nontoxic substance, has been shown to reduce GMCC in animal models of diabetes mellitus. We have now performed a blind placebo controlled study with crossing over of two treatment periods of three months each in 29 patients with diabetes mellitus in order to examine the effect of treatment withL-arginine (2 × 1g daily) on glucose mediated collagen cross links (GMCC). GMCC was evaluated by determining glycosyl lysine (hexosyl lysine) levels in skin punch biopsies. Patients treated byL-arginine showed significantly lower GMCC precursors of skin collagen compared with the placebo treated group (difference of hexosyl lysine as counts/mL/ug hydroxyproline between the first and second skin biopsy 0.11 ± 4.44 vs. 4.03 ± 5.27,t = 2.17,p 〈 0.05). The only side effects ofL-arginine were gastric pain occurring only in patients who did not follow the instructions to takeL-arginine at meals. We conclude thatL-arginine could be useful for treating long term complications of diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    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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