The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.

Exocrine pancreatic function (serum immunoreactive trypsin, fecal chymotrypsin, and pancreatic isoamylase) in Indian diabetics.

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic C-peptide response to oral glucose in fibrocalculous pancreatic diabetes. Improvement after treatment.

beta-Cell function (plasma C-peptide) in 17 fibrocalculous pancreatic diabetic (FCPD) subjects (14 newly diagnosed) was not different at presentation from that in 14 matched insulin-dependent diabetic subjects. After insulin treatment and improvement in the patients' nutritional and metabolic status, fasting and postglucose plasma C-peptide concentrations showed a significant increase (fasting 0.06 +/- 0.01 to 0.17 +/- 0.03 nM, peak 0.11 +/- 0.02 to 0.29 +/- 0.06 nM, mean +/- SE; P less than 0.01 for both). Thus, severely diminished beta-cell function in FCPD is partially reversible after treatment. This could contribute to the clinical metabolic peculiarities of this group of patients.

Serum immunoreactive trypsin in tropical pancreatic diabetes syndrome.

Fifteen patients with tropical pancreatic diabetes syndrome (TPDS), 16 insulin-dependent diabetics (IDD), 27 non-insulin-dependent diabetics (NIDD) and 14 normal subjects, all from India, were investigated for markers of beta-cell (C-peptide) and exocrine (immunoreactive trypsin; IRT) reserve. IRT and C-peptide concentrations were the lowest in TPDS, lower than normal in IDD, and not significantly different from normal in NIDDs. There was a highly significant correlation (rs = 0.93; P less than 0.0001) between IRT and C-peptide (measured in 50% of patients and controls) concentrations when all diabetic groups were combined. Such a correlation was absent when TPDS patients were considered in isolation, largely because of the markedly low IRT concentration. Fourteen of 15 patients (93%) with TPDS had subnormal IRT concentrations, of which 11 had IRT values of less than 50 micrograms/L. These IRT values are similar to those previously reported in cystic fibrosis. Only 6 of 16 IDDs (38%) had subnormal IRT concentrations, of which only one was below 50 micrograms/L. These data suggest that exocrine pancreatic reserve is markedly diminished in TPDS and that a subnormal IRT concentration may be a useful biochemical marker for this form of diabetes.

Altered sensitivity to acetylcholine during chronic administration of organophosphorus anticholinesterase (fenthion) in albino mice.

Tissue sensitivity to acetylcholine during chronic administration of fenthion was assessed in mice. Fenthion was injected intra-muscularly every fourth day and experiments were carried out at various intervals. The parameters selected for testing cholinergic effects were, acetyl choline-induced contraction of isolated ileum and salivary secretion in vivo. In both types of experiments an initial supersensitivity followed by tolerance to acetylcholine were observed. The underlying mechanisms are discussed.