without any significant increase in medication, but attributed to improved lifestyle and improved medication adherence. An extension study was conducted to determine the sustainability of glucose control. Patients were randomized with a ratio of 2:1 favouring intervention; there were no differences in the baseline characteristics of the patients with respect to age, gender, BMI, duration of diabetes, HbA1c or deprivation score. Patients still in the study after 1 year were invited to continue receiving care for a further 2 years, with the original randomization preserved and telecare support continued for the intervention group (in addition to usual care for bothgroups). The primary biomedical outcome variable remained the absolute change in HbA1c, as in the original trial. Changes in HbA1c from baseline to the end of each study year were calculated for each individual and differences between groups were tested using multivariate linear regression, adjusting for age, gender and size of primary care practice. Ethical approval was obtained for this extension study from the NHS Research Ethics Committee (Wrightington, Wigan and Leigh—reference no. 08 ⁄ H1014 ⁄ 25) and from the University of Manchester Research Ethics Committee. The PACCTS trial recruited 591 patients, of whom 501 (85%) entered the extension phase after 1 year. After 3 years, a further 76 patients had withdrawn (13%); there were similar proportions in each group: 47 ⁄ 318 (15%) vs. 29 ⁄ 182 (16%); P = 0.7. Patients with valid measurements for all 3 years (295 vs. 170) were included in the analysis. Table 1 shows mean levels of HbA1c in each group and changes from baseline to each year of follow-up. At the end of the study, there was a statistically significant reduction of HbA1c by 0.24% (confidence interval )0.47 to )0.01, P = 0.041) attributable to intervention. Regression estimates were uninfluenced by age, gender or size of primary care practice. At 3 years, 29.8% of telecare-supported patients reached the target HbA1c of 53 mmol ⁄ mol (7%) compared with 20.3% of usual care patients (P = 0.021). Patient use of medication was classed in a hierarchy from lowest to highest: lifestyle alone; lifestyle + one oral hypoglycaemic drug; lifestyle + two hypoglycaemic drugs; any of the former + insulin. Patients were categorized as having ‘less’ medication if they moved down the treatment hierarchy and ‘more’ if they moved up. There were no treatment group differences at baseline or any year of the study. Comparing baseline and year 3, proportions with less ⁄ same ⁄ more medication were for telecare: 5.8, 66.0 and 28.2% (n = 294); and usual care: 4.5, 70.1 and 25.5% (n = 157), (P = 0.646 v-test for ordered categories). We therefore report that proactive telecare support in addition to usual care demonstrates a continued beneficial effect on glucose control at 3 years. We believe this is clinically relevant, and is likely to be through improved medication compliance and lifestyle measures in the intervention arm, rather than differences in pharmacological interventions between the groups. Although fundamental to managing Type 2 diabetes, lifestyle changes are often difficult to achieve and sustain. The PACCTS intervention achieved improved glycaemic control without additional pharmacological means beyond usual care, and with a trial cohort drawn from a socio-economically deprived urban community. Our work adds more evidence to the application of telemedicine in the management of diabetes and other chronic illnesses [2,3].

AIMS/HYPOTHESIS:People of African origin have increased risk of stroke and retinal microvascular disease compared with populations of European origin. We compared quantitative measures of retinal microvasculature in British white Europeans and African Caribbeans.METHODS:Population-based study of 215 (45% male) British African-Caribbean migrants and 323 (48% male) white Europeans aged 40-69 years. Digitised retinal images were analysed using a validated semi-automated system.RESULTS:Arteriolar optimality deviation, an indicator of endothelial dysfunction, was greater in African Caribbeans (age- and sex-adjusted means [95% CIs]: 0.06 [0.05-0.06] vs 0.04 [0.04-0.05], p = 0.004); this was unexplained by conventional risk factors. Arteriolar diameters were narrower in African Caribbeans (age- and sex-adjusted means [95% CIs]: 18.4 [18.1-18.6] vs 17.9 [17.6-18.2], p = 0.011). These ethnic differences in diameters were attenuated on adjustment for systolic BP (SBP) (adjusted means: 18.2 vs 18.1, p = 0.31). However, there was a significant interaction (p = 0.011) between diabetes and SBP, such that SBP was strongly associated with arteriolar diameter in people without diabetes, but not in those with diabetes (adjusted beta-coefficients for SBP: Europeans: -0.42, p = 0.002 vs 0.17, p = 0.69, African Caribbeans: -0.35, p = 0.023 vs 0.01, p = 0.96). Other measures of retinal vasculature did not differ by ethnicity.CONCLUSIONS/INTERPRETATION:British African Caribbeans appear to have poorer retinal arteriolar endothelial function than white Europeans. Higher BPs explained the narrower arterioles in African Caribbeans; however, patterns of association between arteriolar narrowing and BP suggest the possibility that cerebral autoregulation and/or remodelling might be adversely affected by diabetes in both ethnic groups.

Intensive insulin regimens can produce substantial clinical benefits for patients with type 1 and type 2 diabetes, but they are associated with an increased incidence of hypoglycaemia. This article discusses such regimens and whether the risk of hypoglycaemia can be reduced by using the new basal insulin analogue, insulin glargine.

Background: Measurement of HbA1c is the standard test for assessment of glycaemic control in diabetic subjects. Using new glucose sensing technology we re-evaluated the significance of HbA1c in terms of the aspects of the blood profile it measures in patients with diabetes. Methods: In a group of 27 patients with type 1 diabetes, interstitial fluid glucose concentrations were monitored for a mean of 2·6 days using the Continuous Glucose Monitoring SystemTM (MiniMed Inc, CA, USA). Results were correlated with an HbA1c measurement taken at the time of sensor insertion. Results: Results were available in 25 subjects, two datasets being lost due to patient error. There was a correlation between mean sensor glucose value, and the HbA1c value ( r=0·59, P=0·002). The correlation with standard deviation of the readings was weaker (r=0·3, P=0·15). No other descriptor of the sensor glucose concentration correlated with HbA1c. Conclusion: The mean interstitial glucose concentration recorded with the Continuous Glucose Monitoring System correlates with HbA1c level recorded at the time, but with no other marker of glucose control in diabetic subjects. These results have implications for the interpretation of HbA1c concentrations in type 1 diabetes.

The prevalence of hypertension is particularly high in people of black African descent throughout the world, and the consequences of hypertension, such as hypertensive heart and renal disease and stroke, are also more common. But there is little consensus on whether hypertensive retinopathy follows a similar pattern. We determined the prevalence of hypertensive retinopathy and its relationships with resting and ambulatory blood pressure in a population study of Afro-Caribbeans and Europeans aged 40 to 64 years in London, UK. Retinal photographs of 651 participants were graded for hypertensive retinopathy. Age- and sex-standardized prevalence of retinopathy was 11% (95% confidence interval, 8% to 14%) in Europeans and 21% (95% confidence interval, 16% to 26%) in Afro-Caribbeans ( P <.001), respectively. This ethnic difference in prevalence was greatest in normotensive women (8% in Europeans versus 20% in Afro-Caribbeans, P <.001). Resting systolic pressure was 8 mm Hg higher in normotensive Afro-Caribbean compared with European women, but this could not fully account for the ethnic difference in the prevalence of retinopathy. Examination of the different relationships of age and resting and ambulatory blood pressures with hypertensive retinopathy showed that these relationships were strongest in European women and weakest in Afro-Caribbean women. We conclude that hypertensive retinopathy is more common in Afro-Caribbeans, particularly women, and that ethnic differences in resting blood pressure cannot fully account for this. The relatively weak relationship between resting and ambulatory blood pressures and retinopathy in Afro-Caribbeans suggests that factors other than blood pressure determine the high rates of hypertensive retinopathy in this group.

Journal Article Deficiency of lecithin: cholesterol acyltransferase due to compound heterozygosity of two novel mutations (Gly33Arg and 30 bp ins) in the LCAT gene Get access Heiko Wlebusch, Heiko Wlebusch Search for other works by this author on: Oxford Academic PubMed Google Scholar paul Cullen, paul Cullen * *To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar James S.Owen, James S.Owen 1Department of Clinical Chemistry Search for other works by this author on: Oxford Academic PubMed Google Scholar David Collins, David Collins 2Department of Endocrinology, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJUK Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick S.Sharp, Patrick S.Sharp 2Department of Endocrinology, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJUK Search for other works by this author on: Oxford Academic PubMed Google Scholar Harald Funke, Harald Funke Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerd Assmann Gerd Assmann Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 4, Issue 1, January 1995, Pages 143–145, https://doi.org/10.1093/hmg/4.1.143 Published: 01 January 1995 Article history Received: 11 October 1994 Accepted: 02 November 1994 Published: 01 January 1995

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of L-[1-13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025-0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean +/- SD: 97.8 +/- 24.9 vs 131.0 +/- 23.0 mumol.h-1 x kg-1; p < 0.001), reduced leucine incorporation into protein (80.4 +/- 20.9 vs 108.8 +/- 19.6 mumol.h-1 x kg-1; p < 0.001) and reduced leucine oxidation (17.4 +/- 4.8 vs 22.2 +/- 8.1 mumol.h-1 x kg-1; p < 0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (rho = 0.51, p < 0.05) and leucine incorporation in protein correlated positively with lean body mass (rho = 0.55, p < 0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (rho = 0.71, p < 0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Conference Abstract| July 01 1993 Clinical and Physiological Effects of Biosynthetic Human Growth Hormone Replacement Therapy in Hypopituitary Adults SA Beshyah; SA Beshyah 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar M Shahi; M Shahi 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar V Anyaoku; V Anyaoku 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar E Skinner; E Skinner 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar PS Sharp; PS Sharp 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar R Foale; R Foale 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar DG Johnston DG Johnston 1Unit of Metabolic Medicine and Department of Cardiology, St. Mary's Hospital Medical School, London, W2 1PG, UK (Introduced by Dr D Halliday) Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1993) 85 (s29): 1P. https://doi.org/10.1042/cs085001P Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation SA Beshyah, M Shahi, V Anyaoku, E Skinner, PS Sharp, R Foale, DG Johnston; Clinical and Physiological Effects of Biosynthetic Human Growth Hormone Replacement Therapy in Hypopituitary Adults. Clin Sci (Lond) 1 July 1993; 85 (s29): 1P. doi: https://doi.org/10.1042/cs085001P Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1993 The Biochemical Society and the Medical Research Society1993 Article PDF first page preview Close Modal You do not currently have access to this content.

Adults with hypopituitarism die prematurely, and the excess mortality is from vascular disease. On echocardiography we have demonstrated abnormalities of myocardial diastolic function in hypopituitary adults, indicating possible early ischaemic change. Peripheral arterial disease is evident on ultrasonography. Vascular risk factors have also been examined. Impaired glucose tolerance and unrecognized diabetes are common in hypopituitary adults. Total cholesterol levels are elevated, particularly in hypopituitary women. The role of growth hormone (GH) deficiency in the vascular disease and in the vascular-risk-factor abnormalities is unknown at present. Prolonged GH therapy causes a decrease in the levels of fasting total cholesterol, without any adverse effects on glucose homeostasis. GH therapy trials in adults will clarify the role of GH in the excess vascular risk of hypopituitarism. Prolonged GH therapy will be necessary for the vascular effects to be defined.

OBJECTIVE--To assess cardiac structure and function in patients with treated hypopituitarism and to determine their relation to the degree of growth hormone deficiency and body composition pattern. DESIGN--26 patients with treated hypopituitarism were studied by cross sectional and Doppler echocardiography and by exercise testing. The results were analysed and their relation to the degree of growth hormone deficiency and body composition determined. SETTING--All tests were performed in the department of cardiology and the unit of metabolic medicine at a tertiary referral centre. PATIENTS--Patients with hypopituitarism referred for endocrine assessment. MAIN OUTCOME MEASURES--Left ventricular mass, left ventricular diastolic function, and exercise capacity in patients with hypopituitarism and their relation to growth hormone deficiency. RESULTS--Mean (SD) serum concentration of insulin-like growth factor 1 (IGE-1), a measure of growth hormone deficiency, was 82.4 (45) micrograms/l. Lean body mass calculated by measuring total body potassium was 50 (9) kg. All patients had a normal left ventricular mass index and a normal left ventricular ejection fraction. Eight patients had abnormal left ventricular diastolic function. There was a significant correlation between IGF-1 and left ventricular mass (r = 0.45, p less than 0.02). Lean body mass was also significantly correlated with left ventricular mass (r = 0.78, p less than 0.0001) and left ventricular diastolic function (r = -0.63, p less than 0.01). The mean exercise duration was 8.6 (3.6) minutes. There was a significant correlation between serum IGF-1 and the rate-pressure product on exercise (r = 0.47, p less than 0.01). Seven patients had planar ST segment depression greater than 0.1 mV during exercise testing. In five of these patients there was rapid resolution of ST segment depression immediately after exercise. Two patients developed considerable ST segment depression, and subsequent coronary angiography showed normal coronary arteries. Exercise-induced ST segment depression was not related to the severity or duration of growth hormone deficiency or serum cholesterol concentration. CONCLUSIONS--This study suggests that left ventricular mass and the rate-pressure product are related to the degree of growth hormone deficiency, that left ventricular diastolic dysfunction is frequently seen in hypopituitarism, and that these patients may have ischaemic-like ST segment changes during exercise testing. These findings may explain the increased cardiovascular mortality in patients with hypopituitarism and may also have implications for growth hormone replacement therapy in adults.

Summary. objective Polycystic ovary syndrome (PCOS) Is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of Insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen trans‐port and metabolism In women with PCOS.designWithin‐group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women.patients Forty‐seven women who presented with hirsutlsm, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6±0.7 years (mean±SEM), BMI 27.3±1.2 kgtm2.measurements Plasma Insulin levels were measured at 30‐minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (f T), sex hormone binding globulin (SHBG) and Insulin‐like growth factor‐i (IGF‐I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS Neither basal Insulin nor the sum of Insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with Irregular cycles or amenorrhoea than In those with regular ovule‐tory menses (8.0± 1.1 vs 3.1 ± 1.5 mU/I, P < 0.01) despite similarly raised androgen levels. Both basal Insulin and sumINS correlated with BMI In women with PCO (r=0.37, P < 0.05 and r= 0.64, P < 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF‐I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an Inverse correlation and I T correlated positively with sumINS (r= ‐0.51, P < 0.01; r=0.39, P < 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens.conclusions These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes In SHBG rather than by direct stimulation of ovarian androgen production. Higher Insulin concentrations In anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that Insulin resistance In the ovary contributes to the mechanism of anovulatio in PCOS.

In an analysis of 263 women with polycystic ovary syndrome (PCOS), 91 (35%) of whom were obese (body mass index > 25 kg/m2), it was found that obese women with PCOS were more likely to be anovulatory and had a higher prevalence of hirsutism than the non-obese subgroup. Although serum concentrations of gonadotrophins, androstenedione and total testosterone were similar in obese and lean women with PCO, sex hormone binding globulin (SHBG) levels were significantly lower, and free testosterone correspondingly higher, in obese women. Serum concentrations of SHBG were inversely correlated with those of both fasting and glucose-stimulated insulin. A short-term, very-low-calorie diet resulted in a 2-fold increase in SHBG which was mirrored by a fall in serum insulin. Similar biochemical changes were also observed during a long-term (6–7 months) 1000 kcal diet and were associated with an improvement of menstrual function and fertility. This encourages the view that calorie restriction has an important part to play in the management of obese women with PCOS.

SUMMARY Two hundred and sixty‐three women with ultrasound‐diagnosed polycystic ovary syndrome were studied of whom 91 (35%) were obese (BMI > 25 kg/m 2 ‐). Obese women with PCOS had a greater prevalence of hirsutism (73% compared with 56%) and menstrual disorders than non‐obese subjects. Total testosterone and androstenedione concentrations in serum were similar in the two subgroups but SHBG concentrations were significantly lower, and free testosterone levels higher, in obese compared with lean subjects. In addition, concentrations of androsterone glucuronide, a marker of peripheral 5α‐reductase activity, were higher in obese than in non‐obese women with PCOS. There were no significant correlations of either SHBG or free testosterone with androsterone glucuronide suggesting that obesity has independent effects on transport and on metabolism of androgen. There were no significant differences between the subgroups in either baseline gonadotrophin concentrations or the pulsatile pattern of LH and FSH secretion studied over an 8‐h period. There was, however, an inverse correlation of FSH with BMI, but only in the obese subgroup. In conclusion, the increased frequency of hirsutism in obese compared with lean women with PCOS is associated with increased bio‐availability of androgens to peripheral tissues and enhanced activity of 5α‐reductase in obese subjects. The mechanism underlying the higher prevalence of anovulation in obese women remains unexplained.

Serum insulinlike growth factor-I (IGF-I) concentration was evaluated prospectively over two years in 35 diabetic patients with severe background or preproliferative retinopathy (group 1) and 24 diabetics with mild background retinopathy matched for age, sex, and glycemic control (group 2). In addition, 12 normal subjects were also studied to assess the variability of individual serum IGF-I levels over two years. Mean serum IGF-I (±SD) μg/I at entry, one year, and two years was not significantly different in the patient groups (157 ± 71 v 168 ± 77; 166 ± 78 v 159 ± 87; 143 ± 58 v 159 ± 67) or when compared with the normal subjects (181 ± 47, 188 ± 30; 221 ± 56). Eight patients in the preproliferative group and none in the mild background group developed proliferative retinopathy. In this subgroup developing retinal neovascularization, serum IGF-I at the time of the first appearance of retinal new vessels was significantly higher than 3 months (1 to 4 months) before the onset of proliferation (271 ± 94 v 196 ± 58; P = .036). Values at the time of proliferation were not, however, significantly different from the mean serum IGF-I value of all patients in group 1 and by 4 months (3 to 6 m) had returned to their previous values. Although a transient elevation of IGF-I occurs at the time of retinal new vessel formation, the rise in serum concentration is not sufficiently great or early enough to be of clinical value as a predictor of retinal neovascularization.

The response to GH releasing hormone (GHRH 1-29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 micrograms by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 micrograms/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU.l-1.h-1; 209 +/- 81 vs 121 +/- 82; P = 0.01). Mean +/- SD IGF-I levels (micrograms/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2-16) pump administration (203 +/- 62 vs 60 +/- 25; P = 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)