T. M. Hayes

How soon after myocardial infarction should plasma lipid values be assessed

Because acute myocardial infarction may affect plasma lipid concentrations it is commonly recommended that assessment of these concentrations should be delayed until about three months after the acute event. A study was therefore conducted of fasting plasma lipid concentrations in 58 patients with acute myocardial infarction. Measurements were made during their stay in hospital (days 1, 2, and 9) and three months later. Triglyceride concentrations remained unchanged throughout. Values of total cholesterol, low density lipoprotein, and high density lipoprotein all fell significantly between the first two days and day 9. Total cholesterol and low density lipoprotein also showed significant falls between days 1 and 2. Nevertheless, fasting plasma lipid concentrations showed no significant difference at any time during the first 48 hours from values measured three months later. After the infarction 26 patients changed to eating less fat or less energy, or both. More patients had hypercholesterolaemia in the first 48 hours than at three months. These results suggest that lipid state may be assessed as accurately, and possibly more accurately, during the first 48 hours after acute myocardial infarction than at three months.

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.

The effects of glucose-dependent insulinotropic polypeptide infused at physiological concentrations in normal subjects and Type 2 (non-insulin-dependent) diabetic patients on glucose tolerance and B-cell secretion

SummaryThe effects of porcine glucose-dependent insulinotropic polypeptide given by continuous intravenous infusion in normal subjects (n=6) and Type 2 (non-insulin-dependent) diabetic patients (n=6) have been investigated. The subjects were studied on 2 separate days after overnight fasts. On each day 25 g of glucose was infused from 0–30 min plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (0.75 pmol·kg−1·min−1) or control solution. During the glucose-dependent insulinotropic polypeptide infusion plasma glucose values were reduced in normal subjects from 30–60 min (p<0.01) and in Type 2 diabetic patients at 45 and 60 min (p<0.05). In the normal subjects insulin concentrations were greater from 10–35 min (p<0.01) following glucose-dependent insulinotropic polypeptide infusion and peak values were increased by 123%. In the Type 2 diabetic patients following glucose-dependent insulinotropic polypeptide infusion insulin levels were increased from 4–40 min (p<0.01) but peak values were only increased by 27%. In the normal subjects C-peptide values were greater from 25–45 min (p<0.01) following glucose-dependent insulinotropic polypeptide infusion and peak C-peptide levels were increased by 82%. In the Type 2 diabetic patients following the glucose-dependent insulinotropic polypeptide infusion C-peptide levels were increased from 6–55 min (p<0.01) and peak values were increased by 20%. Plasma glucose-dependent insulinotropic polypeptide levels were within the physiological post prandial range during the glucose-dependent insulinotropic polypeptide infusion. Glucose-dependent insulinotropic polypeptide is insulinotropic in normal subjects and Type 2 diabetic patients at physiological concentrations and results in improved glucose tolerance. This insulinotropic effect is less marked in the diabetic patients and may represent insensitivity of the B cell to glucose-dependent insulinotropic polypeptide.

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 < 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.

Are medical postgraduate certification processes valid? A systematic review of the published evidence

To collate the published works on validation of assessments used in postgraduate medical certification.

The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with Type 2 (non-insulin-dependent) diabetes mellitus

SummaryConsiderable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n=31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n=68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20±3 pmol/l to a peak of 68±5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27±3 pmol/l to a higher peak value of 104±6 pmol/l at 30 min (p<0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30–90 min (p<0.01–0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22±4 pmol/l to a peak of 93±6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25±2 pmol/l to a higher peak of 133±7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p<0.001), 60 min (p<0.01) and from 210–240 min (p<0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.

Effect of somatostatin on renal function

Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.

Human insulin: study of safety and efficacy in man.

The safety and efficacy of a new highly purified neutral soluble human insulin produced by conversion of porcine insulin was compared with a highly purified neutral soluble porcine insulin in six normal men. The insulins were administered by subcutaneous injection at a dose of 0.075 U/kg body weight. Somatostatin was infused during the experiment to suppress endogenous insulin secretin. No difference was found in the plasma glucose, insulin, or metabolite responses. Thus the potency, onset, and duration of effect were identical with the two insulins. No short-term side effects to either insulin were observed. Highly purified, semi-synthetic human insulin offers a safe and effective means to explore the possible advantages of homologous human insulin in the management of diabetes mellitus.

The use of videorecordings of medical postgraduates in improving clinical skills

Summary. The examination for membership of the Royal Colleges of Physicians has a high failure rate despite intensive clinical coaching provided by many postgraduate courses. One of the main difficulties appears to be the failure of candidates to identify specific shortcomings in their clinical behaviour. In this study videorecording was used as a method of self‐appraisal enabling the candidate to identify strengths and weaknesses. The evidence from the study suggests that self‐appraisal by videorecording should be used as an adjunct to clinical instruction.

Screening for Diabetic Retinopathy

There is a need for greater educational emphasis, both at undergraduate and postgraduate level, on the detection of diabetic eye disease, in particular diabetic retinopathy. The early diagnosis of the sight‐threatening lesions of proliferative retinopathy and maculopathy is a prerequisite for the prevention or reduction of the visual loss and blindness associated with this diabetic complication. It is also essential that patients are aware that diabetes can result in visual loss due to diabetic retinopathy. Patients should understand that diabetic retinopathy may be present without ophthalmic or diabetic symptoms and that its incidence increases with duration of diabetes, poor diabetes control, and hypertension. They must also be aware that, if detected early, retinopathy can be treated successfully and vision preserved. Early detection depends on regular eye examination involving both visual acuity assessment and ophthalmoscopy through dilated pupils by experienced personnel. A comprehensive programme of screening followed by prompt and adequate treatment would made a significant contribution to eradicating diabetic retinopathy as a cause of blindness.