Intensive insulin treatment of IDDM is associated with increased frequency of hypoglycemic coma. The extent of possible cerebral sequelae after recovery is still unknown. We studied the impact of previous hypoglycemic coma on neurophysiological measures of cognitive brain function in 108 patients with adult-onset IDDM receiving intensive insulin treatment. In the study, 55 IDDM patients (age 38 +/- 14 years, mean +/- SD) who had a history of > or =1 (median 3, range 1-35) comatose hypoglycemic event were compared with 53 IDDM patients (age 34 +/- 12 years) with no history of hypoglycemic events using P300 event-related potentials and psychometric tests (the Mini-Mental State Exam and trailmaking test, part A). Findings on these patients were compared with those from 108 matched healthy control subjects. No difference was observed in P300 latencies and psychometric tests between patients with and without a history of hypoglycemic coma (P300 latency, 346 vs. 342 ms; trailmaking test, 31 vs. 30 s; Mini-Mental State Exam, 29.5 vs. 29.6; NS). In diabetic patients, however, P300 latencies were delayed compared with those of healthy control subjects (344 vs. 332 ms; P < 0.001) and were correlated to diabetes duration but not to total hypoglycemic episodes. Scores on the Mini-Mental State Exam (29.5 vs. 29.6; P = 0.59) and trailmaking test (31 vs. 28 s; P = 0.10) were not different between patients and control subjects. In conclusion, previous episodes of hypoglycemic coma are not associated with permanent impairment of cognitive brain function in patients with adult-onset IDDM receiving intensive insulin treatment compared with patients without such episodes. Cognitive brain function, however, is subclinically impaired in relation to duration of diabetes.

To determine the impact of both short- and long-term "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%) and D (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).(ABSTRACT TRUNCATED AT 250 WORDS)

To study the potential impact of glucocorticoids on the effects of human atrial natriuretic peptide (hANP) in man, the diuretic and natriuretic response to intravenous bolus doses of hANP (50 and 100 micrograms) was studied in seven male patients with deficient endogenous glucocorticoid synthesis, both during withdrawal of glucocorticoid therapy and during subsequent substitution with dexamethasone. Plasma concentrations of ACTH, though markedly suppressed by dexamethasone as compared to the unsubstituted state were not influenced by exogenous hANP either during deprival or substitution of glucocorticoids. Basal plasma concentrations of hANP were 10.3 +/- 8.4 pmol/l and 19.3 +/- 11.1 pmol/l during glucocorticoid withdrawal and following substitution with dexamethasone, respectively. When substituted with glucocorticoids, patients responded to hANP (100 micrograms) with an increase (p less than 0.025) in diuresis and sodium excretion, whereas no changes in diuresis and sodium excretion were seen following intravenous hANP during glucocorticoid withdrawal. These results suggest that glucocorticoids may have a permissive effect on hANP-mediated natriuresis and diuresis.

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.

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