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Since both acetate and hydrogen are produced by colonic bacterial fermentation, the clinical utility of the measurement of either parameter in nine subjects for the lactulose tolerance test was tested. The fasting plasma acetate concentration (mean +/- s.d., mmol/l) of 0.11 +/- 0.06 increased to peak levels between 150 min (0.23 +/- 0.12) and 180 min (0.23 +/- 0.09), both P less than 0.01, after ingesting 20 g lactulose. In one subject with previous gastrectomy and intestinal hurry, the peak was at 30 min. Mean post-lactulose acetate levels (0.21 +/- 0.09) were higher than fasting levels (P less than 0.03). Breath hydrogen excretion exhibited a similar trend. Indeed, a significant correlation (rs 0.39, P less than 0.01) was demonstrated between the acetate and hydrogen values. It is therefore concluded that patients for the lactulose breath test show fairly similar changes in plasma acetate and breath hydrogen excretion after lactulose ingestion. Either measurement could thus be used in assessing colonic fermentation in humans.

Two hundred and forty-nine patients with non-insulin-dependent diabetes were entered into a prospective study at diagnosis and examined at presentation and one, three, and five years later. Ten years after diagnosis, 34 patients were known to be dead and 214 alive. A number of factors were significantly associated with survival on univariate analysis and appeared to form two independent intra-related groups: a 'metabolic' group and a 'degenerative condition' group. Multivariate analysis of these two groups showed that glucose tolerance (the rate constant KG for decrease in plasma glucose concentration after its intravenous injection) was significantly related to survival in the 'metabolic' group, and age, blood pressure and anti-hypertensive therapy were significant in the 'degenerative' group of factors. A low KG value was more strongly associated with prognosis than any other factor. Values from the one year review were prognostically more useful than initial or later values. Indices of insulin secretion were similar irrespective of whether patients survived or died, and so we believe the lower KG values of dead patients were due to impaired insulin sensitivity. A regression equation using the above factors correctly allocated survival outcome in 81% of subjects.

Serum growth hormone values in 37 patients with diabetic ketoacidosis were 5.4±0.8 ng/ml (S.E.M.) in males and 6.7±1.1 ng/ml in females before treatment; while in five hyperosmolar non-ketotic patients the HGH concentration was 3.9±0.5 ng/ml. One hour after insulin 90% of patients showed a rise in HGH, to a mean of 33.7±9.8 ng/ml for males and 25.5±6.0 ng/ml for females in ketoacidosis; and to 27.1±9.9 ng/ml for hyperosmolar coma patients. The rise, which was transient, was inversely correlated with pretreatment plasma glucose, the l h plasma glucose concentration and plasma urea, and directly proportional to the % fall in blood glucose after 1 h. When the ketoacidosis patients were divided into two groups according to HGH response, those with a small response had the greater disturbances of plasma glucose, blood ketone bodies, blood lactate, plasma urea, blood pH, and blood pressure, the smaller 1 h fall in blood glucose, and the higher mortality. Thus the most severely ketoacidotic patients had the poorest growth hormone response. Growth hormone is probably of little importance as an insulin antagonist in diabetic coma.

Five years after entry into a study prospective from diagnosis of non-insulin-dependent (Type 2) diabetes, 17 patients were known to be dead and 197 alive. On analysis of 136 patients (12 deaths) in whom there was complete information from clinical, metabolic and hormonal examination both before and 1 yr after start of treatment, an index of liability to death within this first 5 yr was calculated, to separate best the dead from the living. One index value correctly ascribed 83% of the dead and 90% of the living (89% of all predictions correct; Youden's "J" value = 0.73). Estimates from the less complete data on the other 78 patients (5 deaths) did not alter the predictive factors. Prediction is more successful with non-cardiac than with cardiac deaths. Five factors contributed to the predictive index for death. One was a long duration of symptoms as recalled at diagnosis. The other 4 factors all came from the 1-yr review (no death then). These were (a) greater glucose intolerance, as expressed by the KG rate constant for disappearance of i.v. injected glucose from the blood (more useful than fasting glucose concentration); (b) higher systolic blood pressure (more useful than diastolic); (c) less obesity, as expressed by the Body Mass Index, and (d) higher fasting blood glycerol concentration. As expected, hyper-glycaemia (as reflected in the KG value) is important, but adrenergic factors may contribute to (a), (b) and (d). From these results earlier diagnosis of this type of diabetes could well be associated with an improved outlook, and in addition this alone might ameliorate the other factors, but measures to normalise them post-diagnosis also require testing.

The possible involvement of growth hormone (GH) and human placental lactogen (HPL) in the development of diabetic tissue damage during pregnancy was studied in 16 insulin-dependent diabetic patients (IDDM), 8 gestational diabetic patients (GD) and 14 normal pregnant women. GH and HPL were elevated in pregnancies complicated by diabetes but, in contrast to the rise of HPL, GH declined throughout pregnancy in all the groups studied. The concentrations of neither correlated with plasma glucose, insulin requirement or duration of diabetes. HPL was positively correlated with urinary albumin excretion (UAE) in all 3 groups, but with blood pressure only in the IDDM group. There was also a significant and positive correlation in all patients between HPL at the end of pregnancy and placental weight. No evidence of serious tissue damage was found in either diabetic group. The vibration sensory threshold was unaffected by pregnancy and was similar to that of normal women. However, in the IDDM group UAE increased significantly postpartum when compared with second trimester values; they also had higher UAE than the other 2 groups post-delivery. A small but significant rise in diastolic blood pressure (DBP) was found in the 3 groups studied between the second and third trimester and pre-delivery. The same trend in systolic blood pressure (SBP) was seen in the diabetic groups. The IDDM had higher systolic and diastolic blood pressures than the normal women at all stages of gestation.

Facial and sublingual temperatures were measured in 61 diabetics undergoing intravenous glucose tolerance tests. Within 2 minutes of starting glucose injection, 58 patients felt warm in the face and trunk, 56 showed a rise in cheek temperature and 23 had visible facial reddening. The most important determinant of cheek temperature rise was initial cheek temperature. Cheek temperature rise was a unimodally distributed variable and was significantly larger in patients with fasting plasma glucose greater than or equal to 6.1 mmol/l than in those with lower glucose (despite similar initial cheek temperatures). Initial cheek temperature correlated with ambient temperature in men with fasting glucose greater than or equal to 6.1 mmol/l but not in those with fasting glucose less than or equal to 6.0 mmol/l nor in women. Initial tongue temperature was also related to ambient temperature in men but not in women and fell following the glucose injection. Although the glucose flush differs from the the chlorpropamide-alcohol flush in its unimodal distribution and relatively small temperature rise, some of the factors which influence reaction could well be considered with benefit in analysis of the chlorpropamide-alcohol flush, in particular the initial cheek (and ambient) temperatures, sex and fasting plasma glucose concentration.

Nine diabetic patients who were receiving various treatments supplemented their normal home diets (two patients) or metabolic ward diets (seven patients) with guar crispbread for five days. Their mean urinary glucose excretion fell significantly by 38% during the last two days. A significant fall in fasting blood glucose concentration of 1.1 +/- 0.4 mmol/1 (19.8 +/- 7.2 mg/100 ml) was seen only in those who took guar after the control period. Over eight weeks' treatment insulin dosage was reduced by 21% in five patients, and home testing showed that glycosuria was reduced by 68% in six patients. Guar crispbread is likely to be a useful adjunct to diabetic treatment irrespective of the type of treatment or insulin dosage used.

Twelve-lead electrocardiograms (ECGs) were recorded at diagnosis from 247 initially non-insulin-requiring diabetics. The record was normal in 208 (84%) patients and abnormal in 39 (16%). The latter were older (p = 0.002), with higher blood pressures (diastolic and systolic) and greater cardiothoracic ratios (all p less than 0.02). They also had higher fasting (p less than 0.01) and post-glucose (p less than 0.04) plasma insulin concentrations per body mass index than those with normal ECGs. Five years later 17 patients had died (4 from proven and 6 from suspected cardiac cause), 5 had sustained a proven myocardial infarct and 3 a suspected cardiac event. ECGs were recorded from 138 patients both at diagnosis and 5 yr later. The record was normal on both occasions in 100 (72%), changed from normal to abnormal in 21 (15%), from abnormal to normal in 9 (7%), and was abnormal on both occasions in 8 (6%). Patients who developed ECG abnormalities were older (p = 0.011), and had greater mean fasting cholesterol during the 5 yr (p = 0.05). They also had greater fasting insulin levels per body mass index both before (mean of initial and 1-yr values, p = 0.02) and after the abnormality developed (p = 0.003) than those with persistently normal recordings. Insulin levels post-glucose were greater at 5 yr in those with cardiac abnormality but, as with the higher diastolic blood pressure and fasting glucose concentration then (both p less than 0.05), this difference was not significant initially. (ABSTRACT TRUNCATED AT 250 WORDS)

At diagnosis of non-insulin-requiring diabetes, in 215 patients, systolic and diastolic (Korotkow 4) blood pressures, corrected for arm circumference, correlated with fasting plasma insulin concentration (r = 0.29, p less than 0.001), body mass index (BMI) (W/H2), and age (p less than 0.05 in all cases for both systolic and diastolic pressures). Women had higher pressures but were also heavier than men. Systolic pressure fell by 13 +/- SD 11%, diastolic by 8 +/- 15%, over 1 month and remained decreased over 5 yr. The fall was greater with high initial pressure (r = 0.6-0.7, p less than 0.001 all years). The correlation of initial pressure with plasma insulin remained significant even when allowing for age, surface area, BMI, and plasma concentrations of glucose, urea, creatinine, sodium and urate. Neither gender nor treatment with sulphonylureas or hypotensives influenced this relationship. During the first 5 yr after diagnosis the correlation between blood pressure and insulin weakened, particularly when allowing for the factors above (at 5 yr, systolic p = 0.025, diastolic NS).

To summarise from some preliminary analyses, a high early insulin: obesity (BMI) ratio remains an associate of later development of ECG change in this diabetic population, and there are reasons to suggest that this may be involved particularly through mechanisms of relative insensitivity to the hypoglycaemic effect of insulin.

Control of diabetes in a group of 82 insulin-treated diabetics was assessed by in-patient 24-hour plasma glucose profiles and haemoglobin A1 (HbA1) estimation. Thirty-two of these patients (39 per cent) had hypoglycaemia (plasma glucose less than or equal to 2 mmol/l) which was rarely associated with symptoms. Twenty-seven (61 per cent) of 44 patients who took a series of out-patient pre-prandial capillary blood samples over a three-day period had hypoglycaemia. Conventional measurements of diabetic control including fasting plasma glucose and HbA1, were lower in patients with hypoglycaemia than in those without. Rebound hyperglycaemia following hypoglycaemia was not seen and its absence was not due to diabetic autonomic neuropathy. Cortisol/creatinine ratios in early morning urine samples were similar in patients with and without nocturnal hypoglycaemia, consistent with the absence or rebound hyperglycaemia. Diabetic retinopathy was less prevalent in patients with hypoglycaemia, possibly reflecting better long-term diabetic control in this group. HbA1 concentration reflects overall blood glucose control in diabetes but near-normal levels must be interpreted with caution since they may be associated with recurrent hypoglycaemia.

Erythrocyte aldehyde dehydrogenase activity (EALDH) was measured in 21 diabetics on long-term chlorpropamide therapy. Median EALDH was 0.362 units, range 0.108 to 0.750 units and correlated neither with previously assessed chlorpropamide alcohol flushing nor with coincident plasma or erythrocyte chlorpropamide concentration. The hypothesis that genetic or permanently acquired reduction in EALDH correlates with CPAF status was not supported. There was no concentration-related inhibition of the enzyme by prevailing plasma or erythrocyte chlorpropamide.

In a series of forty-one episodes of diabetic coma or pre-coma, three patients had plasma potassium values of less than 3.0 mEq/l. All three had been taking thiazide diuretics with only one receiving oral potassium supplements. None was previously known to be diabetic, representing 18% of the new diabetics in the series. The mean plasma potassium for the other new diabetics was 4·7 ± 0·2 mEq/l. These findings emphasize that adequate potassium supplements should be given with thiazide diuretics to diabetic subjects and to those with an increased risk of developing the disease.