PubMed · 7110252
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1982-09-23. Hypoglycemia during exercise.. https://doi.org/10.1056/nejm198209233071317
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This study describes the occurrence of 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one (HMDP) in plasma obtained from normal subjects and patients with type 2 diabetes. We have shown previously that HMDP is a novel hydrophilic hydroperoxide formed in the in vitro Maillard reaction that could be analyzed using ultrasensitive chemiluminescence detection-high-performance liquid chromatography (CL-HPLC). The HMDP concentration was 273+/-227 nmol/l in normal subjects and 656+/-535 nmol/l in patients with diabetes. The HMDP concentration was proportional to the plasma glucose concentration level (r=0.640; P<0.01) but not with the glycated hemoglobin level. To investigate the in vivo effects of HMDP, a range of concentrations of the compound was incubated for different time periods with human serum albumin and lipoproteins. HMDP was found to induce denaturation of these macromolecules by modifying lysine residues and causing cross-linking and polymerization of proteins. In the presence of metal ions such as iron and copper, HMDP induced peroxidative degradation of lipoprotein lipids as measured by an elevation in thiobarbituric acid reactive substances (TBARS) concentration. These results suggested that HMDP is produced as a consequence of both hyperglycemia and increased oxidative stress, and may have the potential to contribute to the pathogenesis of arterial complications in diabetes mellitus.
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Although physicians are confronted with an increasing number of insulin-treated patients with type 2 diabetes mellitus, guidelines for the initial insulin regimen and dose adjustment are rare. If the fasting blood glucose level is > 10 mmol/l and the postprandial values are not much higher than the fasting ones, then the patient can be started on 8-12 IU of an intermediate-acting insulin before going to sleep. In the case of blood glucose levels which increase during the day or if a single insulin dose has insufficient effect, the patient can be started on a twice-daily administration of a premixed insulin. If more than 40 IU of insulin per injection are needed to regulate the blood glucose levels, it might be necessary to switch to administering insulin 4 times per day. Of this total daily quantity, initially 20% is administered as (ultra)short-acting insulin before the three daily meals and 40% as a bedtime intermediate-acting insulin. Occasionally elevated blood glucose levels do not necessarily have to be a reason for adjusting the insulin dosage.