The original criteria described for euglycaemic ketoacidosis (initial blood glucose less than 16.7 mmol/l and plasma bicarbonate equal to or less than 10 mmol/l) were identified in 23 of 722 consecutive episodes (3.2%) of diabetic ketoacidosis. True euglycaemic ketoacidosis (initial blood glucose 10 mmol/l or less) was rare, occurring in 0.8-1.1% of all episodes depending on the defining plasma bicarbonate concentration. Management of euglycaemic ketoacidosis with low-dose continuous intravenous infusion of insulin together with adequate fluid replacement was effective. The clinical and biochemical data did not support the concept of euglycaemic ketoacidosis as a separate entity. The importance of ketone testing rather than glucose testing in the diagnosis of ketoacidosis is, however, emphasized. The importance of adequate insulin and fluid therapy in those few episodes where blood glucose is normal or near normal at presentation is also highlighted.

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Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p < 0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean +/- SEM) of C-peptide (0.75 +/- 0.09 vs 0.52 +/- 0.03 nmol/l, p = 0.07) and immunoradiometrically-determined insulin (60 +/- 12 vs 38 +/- 4 pmol/l, p = 0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3 +/- 2.9 vs 1.6 +/- 0.3 pmol/l, p < 0.01), and 32-33 split proinsulin (7.8 +/- 2.5 vs 2.9 +/- 0.4 pmol/l, p < 0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin:insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20 +/- 5 vs 4 +/- 1%, p < 0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p < 0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroid sex hormones modulate the expression of adipocytokines implicated in the pathogenesis of athero-thrombotic cardiovascular disease. We used exploratory factor analysis to search for latent associations between circulating sex steroid hormones, adipocytokines, and cardiovascular risk factors in a well-characterized cohort of postmenopausal women. Among participants in the Rancho Bernardo community study we identified 515 Caucasian women with a mean age of 74+/-8 years and mean body mass index of 24.2+/-3.7 kg/m(2). All had intact ovaries and none was using estrogen therapy. We constructed models aiming for structural clarity and high loading of variables on individual factors. Total adiponectin loaded with major lipid subfractions (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting triglycerides) and with sex hormone-binding globulin. Leptin loaded with central obesity (waist circumference) and fasting insulin levels. Neither adipocytokine loaded with total or bioavailable testosterone or with estradiol or dehydroepiandrosterone sulfate. Sex hormones consistently loaded together on a separate factor; this co-segregation was not influenced by body mass index. Exclusion of women with diabetes did not alter these observations. In conclusion, we identified evidence of latent associations between adipocytokines and a range of cardiovascular risk factors in postmenopausal women. Our results suggest that cardiovascular risk in older women may be modulated through a hitherto unrecognized association between adiponectin, lipid subfractions, and sex hormone bioavailability.

The responses of circulating intermediary metabolites to a low-dose sequential insulin infusion (basal, 0.005, 0.01, and 0.05 U kg-1 h-1) were assessed in eight non-obese men with Impaired Glucose Tolerance (IGT), and in eight healthy control subjects with normal glucose tolerance matched for age, gender, and body mass index. Fasting hyperinsulinaemia was observed in the subjects with IGT (7.4 +/- 1.0 vs 2.9 +/- 0.3 mU I-1, p less than 0.001). While there was no significant difference (p greater than 0.1) in fasting venous glucose levels between the groups, fasting concentrations of lactate (p less than 0.02), alanine (p less than 0.01), and glycerol (p less than 0.05) were significantly elevated in the subjects with IGT. During the incremental insulin infusion, overall concentrations of glucose (p less than 0.05), lactate (p less than 0.05), alanine (p less than 0.05), glycerol (p less than 0.05), immunoreactive insulin (p less than 0.001), and C-peptide (p less than 0.01) were significantly higher in the subjects with IGT. Linear dose-response relationships (p less than 0.005) for circulating immunoreactive insulin (log) vs metabolite concentrations were demonstrated by analysis of variance for glucose, non-esterified fatty acids (NEFA), glycerol, and total ketone bodies. For glucose, glycerol, and NEFA, group dose-response regression lines for the subjects with IGT were displaced significantly to the right (p less than 0.001 for each) of those for the normal control subjects, implying insulin insensitivity. In addition to the recognized defect in glucose homeostasis, these results indicate impaired regulation of multiple aspects of intermediary metabolism including lipolysis in IGT.