A sensitive assay was used to measure the binding of iodine-125-labeled insulin in serum obtained from 112 newly diagnosed insulin-dependent diabetics before insulin treatment was initiated. Two groups of nondiabetics served as controls: children with a variety of diseases other than diabetes and nondiabetic siblings of insulin-dependent diabetics. Eighteen of the diabetics were found to have elevated binding and 36 were above the 95th percentile of control values. The insulin-binding protein is precipitated by antibody to human immunoglobulin G, has a displacement curve that is parallel and over the same concentration range as serum from long-standing insulin-dependent diabetics, and elutes from a Sephacryl S-300 column at the position of gamma globulin. These insulin antibodies are present in a large percentage of newly diagnosed, untreated diabetics and may be an immune marker of B-cell damage.

A B S T R A C T The close anatomical relationships between pancreatic alpha and beta cells makes possible their interaction at a local (paracrine) level. To demonstrate this in vivo, we have compared the acute glucagon response to intravenous arginine in the basal state and after beta cell suppression by infusions of insulin. The plasma glucose concentration was maintained by the glucose clamp technique. In six normal weight nondiabetics, infusion of insulin at 0.2 mU/kg per min (rate 1) raised the mean±SEM plasma insulin levels from 10±3 to 32±4 mU/liter and at 1 mU/kg per min (rate 2) raised plasma insulin to 84±8 mU/liter. This resulted in beta cell suppression, as shown by a diminution in the acute insulin response (incremental area under the insulin response curve, 0-10 min): basal = 283+61, 199±66 (rate 1) and 143±48 mU/liter per 10 min (rate 2) and a fall in prestimulus C-peptide from 1.05±0.17 to 0.66±0.15 and to 0.44±0.15 nM/liter (all P < 0.01). This beta cell suppression was associated with increased glucagon responses to arginine: 573±75 (basal), 829±114 (rate 1), and 994±136 ng/liter per 10 min (rate 2) and increased peak glucagon responses 181±11 (basal), 214±16 (rate 1), and 259±29 ng/liter (rate 2) (all P < 0.01). In all subjects, there was a proportional change between the rise in the acute glucagon response to arginine and the fall in the prearginine C-peptide level. To demonstrate that augmented glucagon response was due to beta cell suppression, and not to the metabolic effect of infused insulin, similar studies were performed in C-peptide-negative-diabetics. Their acute glucagon response to arginine was

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

The ability of psyllium fiber to reduce postprandial serum glucose and insulin concentrations was studied in 18 non-insulin-dependent diabetic patients in a crossover design. Psyllium fiber or placebo was administered twice during each 15-h crossover phase, immediately before breakfast and dinner. No psyllium fiber or placebo was given at lunch, which allowed measurement of residual or second-meal effects. For meals eaten immediately after psyllium ingestion, maximum postprandial glucose elevation was reduced by 14% at breakfast and 20% at dinner relative to placebo. Postprandial serum insulin concentrations measured after breakfast were reduced by 12% relative to placebo. Second-meal effects after lunch showed a 31% reduction in postprandial glucose elevation relative to placebo. No significant differences in effects were noted between patients whose diabetes was controlled by diet alone and those whose diabetes was controlled by oral hypoglycemic drugs. Results indicate that psyllium as a meal supplement reduces proximate and second-meal postprandial glucose and insulin concentrations in non-insulin-dependent diabetics.