Normo-osmolar, nonketotic, hyponatremic diabetic syndrome associated with impaired renal function.

A case is reported of a nonketotic woman with diabetes who presented with a blood glucose of 72.8 mmol/L (1310 mg/dl), plasma sodium of 92 mmol/L, normal osmolality, impaired renal function, and alert clinical state. Before the implication of the unusual nature of the metabolic disturbance was fully considered, the initial treatment was with a rapid infusion of saline. On consideration, however, it was postulated that as her hyperglycemia had developed, the expected osmotic diuresis was prevented by the impairment of her renal function. This had allowed compensatory hyponatremia to develop to maintain normal osmolality and protect the patient from coma. The high-dose saline infusion was stopped, and she was successfully treated with insulin and potassium but only minimal saline. The use of large quantities of saline in normo-osmolar, nonketotic, hyponatremic diabetic syndrome associated with impaired renal function and alert mental state is unnecessary and potentially dangerous.

Assessment of diabetic control: a comparison between home and clinic blood glucose levels.

A comparison between blood glucose levels in patients attending a diabetes clinic and in the same patients leading their normal lives showed that for maturity-onset diabetic patients on oral hypoglycemic therapy, the clinic levels were a poor guide to the patients' usual blood glucose. For insulin-treated patients and for those treated with diet alone, the clinic levels were not significantly different from those taken at home or work.

Glycosylated serum albumin: an intermediate index of diabetic control.

Glycosylated hemoglobin (HbA1) is widely used as an index of glycemic control in diabetic patients. However, due to the long survival time of erythrocytes (120 days), it remains elevated for several weeks after improved control. Other plasma proteins are similarly glycosylated, and as glycosylated serum albumin (GSA) has a shorter half-life (20 days), it should detect glycemic changes earlier. Fasting blood glucose (FBG), GSA, and HbA1 were measured weekly in newly diagnosed diabetic patients (N = 12) for 8 wk after beginning treatment. After 4 wk, a similar fall in FBG and GSA levels, i.e., 72% and 58% respectively, was observed. In contrast, HbA1 fell significantly less (P less than 0.01), by only 39% of its initial value. By 8 wk there was no significant difference between the percentage reduction in the three indices of control. Therefore, GSA provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention and can be regarded as an intermediate index of diabetic control.

The clinical pharmacology of human insulin (Novo) in normal subjects.

Neutral regular human insulin (Novo) (derived from porcine insulin) and porcine insulin were administered by subcutaneous (s.c.) injection into the anterior abdominal wall in two different groups of six normal male subjects. The insulin dosage was 0.075 IU/kg body wt; diluting medium was used to obtain control values. In one group, somatostatin was administered by continuous intravenous infusion (100 micrograms/h) to inhibit pancreatic beta-cell secretion. The plasma glucose, C-peptide, and insulin (immunoreactive) responses to human insulin and porcine insulin were identical in the studies with and without somatostatin. Although the incremental plasma insulin values achieved with the two insulins were similar in the two studies, the hypoglycemic effect was accentuated in the presence of somatostatin, with a delayed recovery toward normoglycemia. The human insulin and porcine insulin were well tolerated in all subjects and there were no unwanted side effects.

Dawn phenomenon: its frequency in non-insulin-dependent diabetic patients on conventional therapy.

The frequency of the dawn phenomenon has been studied in non-insulin-dependent diabetic (NIDDM) patients while they continued with their conventional therapy. Plasma glucose (PG) and immunoreactive insulin (IRI) were estimated hourly from 0300 to 0900 h in 19 NIDDM patients; 9 patients were treated by diet alone (group 1), and 10 patients were treated by diet and oral hypoglycemic agents (group 2). The dawn rise of plasma glucose was demonstrated in 17 (89.5%) of the 19 patients with mean +/- SE plasma glucose at 0300 h of 7.0 +/- 0.5 mM and at 0800 h of 8.4 +/- 0.6 (P less than .01). IRI in all patients rose from 14.7 +/- 1.3 microU/ml at 0500 h to 18.1 +/- 1.8 microU/ml at 0700 h (P less than .05). The changes in IRI levels at any time from 0300 to 0800 h in groups 1 and 2 when considered separately were insignificant. Thus, the dawn phenomenon occurs commonly in NIDDM patients taking their conventional therapy.

Renal response to intravenous somatostatin in insulin-dependent diabetic patients and normal subjects.

The acute effects of iv somatostatin (SRIH; 100 micrograms/h) on the urinary flow (Uvol), effective renal plasma flow (RPF), and glomerular filtration rate (GFR) were compared with those of a control infusion of 0.15 M NaCl in nine insulin-dependent diabetic (IDD) patients of less than 10 yr disease duration and six normal subjects (NS). RPF and GFR were measured using a standard primed constant isotope infusion of [125I]iodohippurate and [51Cr]chromium EDTA. Uvol, RPF, and GFR were measured during 20-min clearance periods. During the NaCl infusion mean Uvol, RPF, and GFR were 14.1 +/- 0.2 (+/- SEM), 708 +/- 4, and 150 +/- 1 mL/min in the IDD group and 12.7 +/- 0.4, 568 +/- 5, and 110 +/- 2 mL/min in the NS group, respectively. In the IDD patients Uvol, RPF, and GFR decreased from 16.6 +/- 1.8, 670 +/- 30, 146 +/- 4 mL/min pre-SRIH to 9.2 +/- 1 (P less than 0.001), 553 +/- 25 (P less than 0.001), and 130 +/- 5 (P less than 0.001) mL/min, respectively, at 120 min during the SRIH infusion. Similarly, in the NS group mean Uvol, RPF, and GFR were 14.2 +/- 0.6, 552 +/- 15, and 112 +/- 5 mL/min pre-SRIH and decreased to 7.4 +/- 0.6 (P less than 0.001), 422 +/- 7 (P less than 0.001), and 93 +/- 3 (P less than 0.001) mL/min, respectively, after 120 min of the SRIH infusion. SRIH, therefore, had a profound effect on renal function in both IDD patients and NS, resulting in a reduction in RPF, GFR, and, as a consequence, Uvol.

Dietary determinants of lipoproteins, total cholesterol, viscosity, fibrinogen, and blood pressure.

High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, viscosity, fibrinogen, and blood pressure were determined in 117 men aged 44 to 60 yr selected from the general population who also completed 7-day weighed dietary records. Associations between these measurements and a number of dietary factors were assessed by multiple regression analysis, allowing where necessary for the effects of age, body mass index, and smoking habit. High-density lipoprotein cholesterol was associated positively with both alcohol and fish consumption and negatively with saturated fat intake. High-density lipoprotein cholesterol expressed as a percentage of total cholesterol was associated negatively with the percentage of energy from fat and positively with fish consumption. Low-density lipoprotein cholesterol was associated positively with the percentage of energy from fat and negatively with fish consumption. Fibrinogen and systolic blood pressure were inversely related to cereal fiber intake.

Candidal infections and populations of Candida albicans in mouths of diabetics.

The prevalence of oral candidosis and the frequency of isolation of Candida albicans and its density and distribution have been determined in the mouths of 50 patients with diabetes mellitus and 50 healthy volunteers matched for age, sex, dental status and smoking habits. Three of the diabetic patients were found to have a chronic oral candidosis. According to an imprint culture technique, the oral carrier rate and density of C albicans were both higher in the diabetic group as a whole than in the control subjects. Smoking was associated with an increased prevalence of the yeast in diabetes mellitus. Diabetics wearing dentures had higher candidal density than those without a prosthesis. No differences in candidal status could be detected according to the degree of control of diabetes, mode of treatment, duration of diabetes or the patient's age. Local factors such as smoking and the presence of dentures, particularly when worn continuously, interact with diabetes mellitus in promoting candidal colonisation of the mouth. Attention to these predisposing factors could reduce the incidence of thrush in diabetics.

Determinants of high density lipoprotein and total cholesterol in women.

An epidemiological study was carried out among a random sample of women aged 18 to 69 years to examine possible determinants of plasma high density lipoprotein and total cholesterol (HDL-C and T-C). In a multiple regression analysis consumption of alcohol, fatty fish, and parental longevity showed positive associations with HDL-C, which were statistically significant. Smoking habit, sucrose consumption, and a family history of ischaemic heart disease showed significantly negative associations. In contrast, T-C was associated significantly only with age and Quetelet's index of body mass. Five variables having significant associations with HDL-C explained only 8% of the total variance; in the case of T-C 17% of the variance was explained by age and body mass.

Determinants of plasma lipoproteins and coagulation factors in men from Caerphilly, South Wales.

Dietary, social, and constitutional determinants of plasma concentrations of some major risk factors for ischaemic heart disease were investigated in a cross sectional study among 711 men from the general population aged 30-69. For high density lipoprotein cholesterol (HDL-C) six variables were significantly associated with plasma concentrations, and these variables explained 12.6% of the variance. For low density lipoprotein cholesterol (LDL-C), total cholesterol (T-C), and triglyceride 8.4%, 7.5%, and 18.5% of the variance was explained by significantly associated variables. Fibrinogen concentrations determined chemically were significantly associated with age, smoking habit, body mass index, alcohol consumption, and intake of cereal fibre (24.2% variance). These data provide some encouragement for the possibility of dietary intervention to influence plasma concentrations of major risk factors for ischaemic heart disease in men.

Associations of alcohol consumption with plasma high density lipoprotein cholesterol and its major subfractions: the Caerphilly and Speedwell Collaborative Heart Disease Studies.

In surveys of 4860 middle-aged men in Caerphilly (South Wales) and Speedwell (Bristol) alcohol consumption has been related to high density lipoprotein (HDL) cholesterol and its major subfractions, HDL2 and HDL3, measured in a single fasting blood sample. The results confirm that high density lipoprotein cholesterol concentration increases as the amount of alcohol regularly consumed increases. The relationship appears to be linear and is independent of age, smoking habit, body mass index, low density lipoprotein cholesterol and plasma total triglyceride. This rise in HDL cholesterol is not mediated through either HDL2 cholesterol or HDL3 cholesterol alone. Both subclasses increase significantly and by similar amounts with increasing alcohol intake.

A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the beta cell response or glucose tolerance in type 2 diabetes mellitus.

Newly diagnosed, previously untreated patients with type 2 diabetes mellitus (n = 6) were studied on two separate days after overnight fasts. On each day they were given a 500-kcal mixed meal plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (GIP) (0.75 pmol/kg/min) or control solution (CS) from 0 to 30 min in random order. Frequent measurements of plasma glucose, C-peptide, insulin and GIP concentrations were made. Fasting GIP levels were similar on both days. During the meal plus GIP infusion plasma GIP levels increased from a basal value of 7.6 +/- 1.5 pmol/1 to a peak of 88.6 +/- 5.4 pmol/1 at 30 min. Following the meal infusion of CS GIP increased from a fasting level of 10.3 +/- 1.2 pmol/1 to a significantly lower peak of 58.0 +/- 8.3 pmol/1 at 60 min. During the meal plus GIP infusion GIP levels were higher at 10-45 min and at 90 min (P less than 0.05-0.001). Fasting and postprandial glucose, C-peptide and insulin levels were, however, similar on both study day. A supplementary infusion of porcine GIP with a mixed meal did not significantly alter the beta cell response or glucose tolerance in this group of patients with type 2 diabetes mellitus.

Non-insulin-dependent diabetic patients (NIDDMs) do not demonstrate the dawn phenomenon at presentation.

A dawn rise of plasma glucose (PG) and/or insulin, the 'dawn phenomenon', has been commonly reported in treated diabetic patients and normal subjects. To evaluate the effect of treatment on this phenomenon in non-insulin-dependent diabetics (NIDDMs), PG, C peptide, immunoreactive insulin (IRI), growth hormone (GH), cortisol, epinephrine, and norepinephrine were measured hourly between 24.00 and 09.00 h in 17 newly diagnosed untreated NIDDMs (group 1). The study was repeated in 11 patients after a year of treatment (group 2). The PG levels did not change significantly at any time from 03.00 to 08.00 h in group 1 but increased continuously from 6.7 +/- 0.5 mmol/l at 04.00 h to 7.8 +/- 0.5 mmol/l at 08.00 h (P less than 0.01) in group 2. IRI and C peptide decreased significantly after 07.00 h in both groups. GH and catecholamine changes were similar in group 1 and group 2. Cortisol levels showed a nadir at 02.00 h and a peak after 07.00 h in both groups. Our results demonstrate no dawn rise of mean PG, IRI and C peptide in newly diagnosed untreated NIDDMs but a significant rise of PG in the early morning period in NIDDMs after a year of treatment with diet alone and diet plus sulphonylureas. Therefore other factors such as treatment and/or duration of the diabetes may play an important role in the pathogenesis of the dawn phenomenon.

Continuing education for general practice and the role of the pharmaceutical industry.

A survey of the involvement in and attitudes towards continuing medical education of 101 general practitioners achieved a 95% response rate. Ninety per cent of the 96 doctors worked in practices which held meetings the content of which was organized by representatives of pharmaceutical companies but only 46% worked in practices which organized their own educational meetings. Seventy six per cent attended meetings away from their practice which were organized by drug companies and 75% had attended at some time continuing medical education activities organized by a local postgraduate centre. The promotional aspects of the drug company organized meetings were disliked by a majority of respondents (58%); more of the trainers (62%) and more of those who had entered general practice within the last seven years (71%) disliked this aspect. Nonetheless the educational content of both meetings held in the practice and those held elsewhere was the aspect most liked by over half of the respondents (59% and 53% respectively). Only 16% of all respondents thought that visits by representatives from pharmaceutical companies were educationally valuable and 37% thought that educational events organized by these companies were of value. Surprisingly 60% of those who worked in practices which held meetings organized by drug company representatives thought them to be of little or no educational value. There is clearly a need for practice based continuing medical education but the current level of dependence on drug companies for organizing these meetings must be questioned. Alternative strategies for the provision of independent non-sponsored educational activities should be sought.

Continuing medical education: a personal view.

Over many generations doctors have kept up to date in ways which reflect their own learning styles. The current fashion for formalised and policed continuing medical education may prove ineffective unless it is recognised that individual needs must be taken into account. Attendance at formal courses based on lectures and papers may not suit a large proportion of those who attend to acquire the necessary points to satisfy their royal college. The ability to show that health care teams are up to date should come from effective clinical audit, which should also identify local educational needs.

General practitioners' continuing medical education within and outside their practice.

To study continuing medical education 96 out of 101 general practitioners chosen at random from the list held by a family practitioner committee were interviewed. The results provided little evidence of regular attendance at local postgraduate centre meetings, though practice based educational meetings were common. Thirty one of the general practitioners worked in practices that held one or more practice based educational meetings each month at which the doctors provided the main educational content. Performance review was undertaken in the practices of 51 of the general practitioners, and 80 of the doctors recognised its value. The general practitioners considered that the most valuable educational activities occurred within the practice, the most valued being contact with partners. They asked for increased contact with hospital doctors. The development of general practitioners' continuing medical education should be based on the content of the individual general practitioner's day to day work and entail contact with his or her professional colleagues.

Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation: no causal relation with diabetic autonomic neuropathy.

OBJECTIVE: To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN: Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING: One routine diabetic unit in a university teaching hospital. PATIENTS: 23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES: Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS: There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS: Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.