An assessment of insulin action in hyperosmolar hyperglycemic nonketotic diabetic patients.

The effect of insulin treatment on the rate of decline of plasma glucose concentration was determined in nine patients with hyperosmolar hyperglycemic nonketosis [HHNK; mean plasma glucose, 999 +/- 59 (+/- SEM) mg/dl] and in six normal subjects rendered hyperglycemic by a combined infusion of somatostatin and glucose (mean plasma glucose, 653 +/- 28 mg/dl). Both the fractional glucose turnover and the half-time of the fall in plasma glucose during low dose (5-10 U/h) insulin treatment were reduced 10-fold (P less than 0.001) in the diabetic patients compared with the hyperglycemic normal subjects. In the hyperosmolar patients, the mean glucose clearance during insulin treatment was only 7% that in the normal subjects (P less than 0.001). The rate of plasma glucose decline in our hyperosmolar patients after hydration and insulin administration was 80 +/- 7 mg/dl X h. This decline is comparable to the results reported in other series, although in striking contrast to the 508 +/- 32 mg/dl X h decline in normal subjects (P less than 0.001). Our findings do not support the clinical impression that HHNK patients are insulin sensitive. We conclude that marked resistance to infused insulin delays the correction of hyperglycemia during treatment of HHNK and suggest that resistance to the normal basal insulin levels encountered in some HHNK patients may contribute in part to the development of the hyperosmolar state.

Diabetes enhances activity of alanine transport in liver plasma membrane vesicles.

In the present study plasma membrane vesicles were prepared from livers of control and alloxan-induced diabetic rats and the substrate specificity and kinetic characteristics of alanine transport determined in both groups. Sodium-dependent alanine uptake at physiological alanine concentrations (100 microM) was enhanced threefold in diabetic as compared with control animals (0.31 +/- 0.04 vs. 0.11 +/- 0.01 nmol X mg protein-1 X 10 s-1). This accelerated influx corresponded to a three- to fourfold increase in the Vmax of alanine transport in diabetic versus control group (7.1 +/- 2.1 vs. 1.6 +/- 0.2 nmol X mg protein-1 X 10 s-1, P less than 0.05), whereas the Km of alanine uptake was unchanged (2.8 +/- 1.2 vs. 1.4 +/- 0.1 mM). Other neutral amino acids (20 mM) inhibited alanine transport to a similar degree in both groups. The sodium-dependent influx of glutamine (100 microM) was similar in diabetic and control groups (0.17 +/- 0.03 and 0.14 +/- 0.02 nmol X mg protein-1 X 10 s-1, respectively). The initial velocity of 22Na uptake (80 mM) into vesicles and half-maximal stimulation of alanine transport was achieved at essentially identical sodium concentrations (approximately 40 mM) in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects.

BACKGROUND: Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN. METHODS: This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks. RESULTS: Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (-2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control. CONCLUSIONS: Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.