J. P. Vora

Non-mydriatic Polaroid photography in screening for diabetic retinopathy: evaluation in a clinical setting.

Because of fears that Polaroid colour prints produced with a non-mydriatic fundus camera may not detect important sight threatening lesions in diabetes a study was conducted comparing retinal images obtained on Polaroid prints taken in “field” conditions with those on 35 mm transparencies and fluorescein angiograms. Almost one in five (22/127) Polaroid prints could not be assessed owing to poor quality compared with 3 (2.4%) 35 mm transparencies and 2 (1.6%) fluorescein angiograms. The pick up rate of microaneurysms, haemorrhages, and hard and soft (cotton wool spots) exudates was equivalent for Polaroid prints and 35 mm transparencies of equivalent quality. In two cases with disc new vessels, however, these were not seen on the Polaroid prints. The widespread use of Polaroid colour prints obtained with a non-mydriatic camera without the necessary operative and interpretive skills further limits the usefulness of the technique.

Impact of initial treatment on renal function in newly-diagnosed type 2 (non-insulin-dependent) diabetes mellitus.

SummaryThe impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p<0.01); fasting plasma glucose (p<0.001); glycated haemoglobin (HbA1) (p<0.001); systolic blood pressure (p<0.01); and diastolic blood pressure (p<0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min−1 (p<0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min−1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) μg·min−1 (p<0.01). Changes in glomerular filtration rate (Δ values) were inversely correlated with presentation values (p<0.001), and positive relationships were observed with Δ effective renal plasma flow (p<0.01), and Δ glycated haemoglobin (p<0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min−1 demonstrated significant reduction in glomerular filtration rate (n=31; p<0.001), whilst those with original values less than 120 ml·min−1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p<0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p<0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min−1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. CONCLUSIONS--The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.

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.

Absorption of Radiolabeled Soluble Insulin in Type 1 (Insulin-dependent) Diabetes: Influence of Subcutaneous Blood Flow and Anthropometry

The rate of absorption of soluble insulin, and its relationships with subcutaneous blood flow (SCBF) and patients anthropometry, were investigated in 12 male Type 1 (insulin‐dependent) diabetic patients of less than 10 yr disease duration (age range: 23–29 yr; body mass index (BMI): 22.2–30.8 kg m−2). Simultaneous assessment of the absorption of 125I‐labelled soluble insulin and SCBF (99mTechnetium clearance) were performed, on separate study days, for the anterior abdominal wall, anterior mid‐thigh, and the upper arm injection sites. Absorption of 125I soluble insulin, including during the lag‐phase, was determined by the two‐ and three‐parameters biexponential models description of residual radioactivity levels at the injection site. Anthropometric measurements utilized were: BMI, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skinfold thickness at anterior abdominal wall, biceps, triceps, anterior mid‐thigh and subscapular sites. Rate‐constants for absorption of soluble insulin were positively correlated with SCBF (Spearman rank coefficient (rs) = 0.33‐0.55; p < 0.01‐0.001). An inverse relationship was observed between the duration of the lag‐phase and SCBF (rs = −0.28‐ −0.54; p < 0.05‐0.001). Patients degree of adiposity was inversely correlated with the rate of soluble insulin absorption (rs = −0.24‐ −0.28; p < 0.05) and SCBF (rs = −0.28‐ −0.43; p < 0.05‐0.001). Consequently, faster absorption of soluble insulin, with shorter lag‐phase duration, was noted for the abdominal and thigh sites for non‐obese (BMI > 25 kg m−2) than obese patients (BMK 27.5 kg m−2) (p < 0.05–0.01). In Type 1 (insulin‐dependent) diabetic patients, the rate of absorption of soluble insulin, including during the lag‐phase, is positively correlated with subcutaneous blood flow. Increasing adiposity prolongs the duration of the early lag‐phase and reduces the rate of absorption of soluble insulin and subcutaneous blood flow.

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.

Simultaneous determination of glomerular filtration rate and effective renal plasma flow.

A method is described for the simultaneous determination of GFR and ERPF within the normal range using a single injection of 51Cr-EDTA and 125I-OIH. Reference values of GFR (range 59-176 ml min-1) and ERPF (268-810 ml min-1) were calculated from bi-exponential analysis of curves based on multiple plasma samples. A subset of the samples (44, 120, 180 and 240 min) was used to estimate GFR by fitting a bi-exponential curve. Regression analysis demonstrated that the reference GFR value could be predicted from this four-sample estimate with a standard error of estimate (SEE) of 2.9 ml min-1, which compared favourably with methods based on mono-exponential analysis (minimum SEE = 6.3 ml min-1) or single samples (minimum SEE = 7.7 ml min-1). The effective volume of distribution of 125I-OIH calculated from the 44 min sample was used to estimate ERPF using a published equation with a SEE of 52 ml min-1. The improved precision of this simplified method for the simultaneous measurement of GFR and ERPF in the normal range will facilitate longitudinal studies in large patient groups in the evaluation of the causative factors of renal disease.

Human, Porcine and Bovine Ultralente Insulin: Subcutaneous Administration in Normal Man

Six normal subjects received subcutaneous human, porcine, and bovine ultralente insulin (0.30 U/kg) and diluent (control) in randomized order. Plasma glucose, C‐peptide, and insulin were measured for 32 h after injection. From 10 h onward human ultralente produced significantly lower plasma glucose levels (p<0.05‐0.01) compared to bovine ultralente. Porcine ultralente produced an intermediate hypoglycaemic response up to 16 h and was similar to the bovine insulin from 24–32 h. Estimated exogenous insulin concentration was higher (p<0.05‐0.001) following human ultralente compared to bovine ultralente between 2 and 22 h after injection. Up to 24 h the porcine preparation led to intermediate insulin levels, but becoming identical to bovine ultralente from 28–32 h. Peak mean exogenous insulin values for human, porcine, and bovine ultralente were 0.054, 0.044, and 0.023 nmol/l at 14, 16, and 18 h, respectively, reaching 0.022, 0.013, and 0.013 nmol/l at 32 h. The different pharmacokinetic behaviour of human and bovine ultralente insulin must be considered when initiating treatment with human ultralente or transferring patients from bovine to human ultralente.

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.

Preservation of Renal Haemodynamic Response to an Oral Protein Load in Non‐insulin‐dependent Diabetes Mellitus

Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were determined, for 2h prior to and 3h following the ingestion of a 1.2 g kg−1 meat meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting good glycaemic control (fasting plasma glucose (mean ± SD): 7.2 ± 2.0 mmol l−1; glycosylated haemoglobin: 8.1 ± 1.7%) and in nine normal subjects selected for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface area) were 83 ± 10 and 410 ± 76 ml min−1 for the Type 2 diabetic patients and 86 ± 11 and 405 ± 113 ml min−1 for the normals. GFR increased by 38 ± 8 and 32 ± 15% in the diabetic patients and normals, to 108 ± 25 and 105 ± 26 ml min−1 (p < 0.01 vs baseline). Peak ERPF was 501 ± 127 and 476 ± 119 ml min−1 for the two respective groups (p < 0.01 vs baseline). Filtration fractions at peak GFR and EPRF values were unchanged from baseline for either groups. Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in normals, results in an acute elevation of GFR. Absolute and incremental changes in GFR were identical for the two groups. These data demonstrate a preserved capacity for renal vasodilatation in Type 2 diabetic patients despite their greater chronological age.