bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated serum TNF‐α level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients
Authors: Winkler G. , Lakatos P. , Salamon F. , Nagy Z. , Speer G. , Kovács M. , Harmos G. , Dworak O. , Cseh K.
Published: March 2003

Aims The aim of the study was to analyse the role of tumour necrosis factor‐alpha (TNF‐α) in insulin resistance and endothelial dysfunction in patients with different types of obesity.

Patients and methods Fasting serum TNF‐α immunoreactive concentration (enzyme‐linked immunosorbent assay, ELISA) and bioactivity (L929 cell cytotoxicity assay), endothelin‐1 and C‐peptide levels (radioimmunoassay, RIA) were measured in 15 patients with android‐ and 13 patients with gynoid‐type obesity and 15 lean healthy controls with normal glucose tolerance and blood pressure.

Results Significantly (P< 0.01) higher TNF‐α concentration (8.92 ± 0.44 pg/ml) and bioactivity (3.12 ± 0.48 U/ml) were found in patients with android obesity as compared to patients with gynoid obesity (7.01 ± 0.30 pg/ml, 0.97 ± 0.11 U/ml) and to the lean controls (6.88 ± 0.26 pg/ml, 0.88 ± 0.08 U/ml). Serum endothelin‐1 (5.38 ± 0.30 pg/ml) and C‐peptide levels (4.82 ± 0.71 ng/ml) were also significantly higher (P < 0.01) in patients with android‐type obesity than in controls (3.89 ± 0.43 pg/ml, 1.46 ± 0.25 ng/ml, respectively). In patients with gynoid‐type obesity, only the C‐peptide levels proved to be significantly higher (2.84 ± 0.29 ng/ml). Endothelin‐1 levels, although were found to be slightly higher, did not differ statistically from in controls (4.56 ± 0.31 pg/ml). There were significant positive linear correlations only in patients with android‐type obesity between TNF‐α, body mass index (BMI), serum endothelin‐1 and C‐peptide levels.

Conclusions TNF‐α may be one of the factors contributing to insulin resistance and vascular dysfunction in patients with android obesity.

Diabet. Med. 16, 207–211 (1999)
Potential impact of a change in the diagnostic criteria for diabetes mellitus on the prevalence of abnormal glucose tolerance in a local community at risk of diabetes: impact of new diagnostic criteria for diabetes mellitus
Authors: Davies M. J. , Muehlbayer S. , Garrick P. , McNally P. G.
Published: March 2003

Aims To compare the prevalence of diabetes and abnormal glucose metabolism using conventional and suggested new WHO and new ADA criteria in a group of people with symptoms of diabetes.

Methods We examined retrospectively the results of 154 consecutive OGTTs in such patients performed using capillary whole blood.

Results With the 1985 WHO criteria. Forty‐four point eight per cent of subjects (69 subjects, with 95% confidence intervals, 37–52.6%) had diabetes, 47.8% (33 subjects, 36–59.6%) had a normal fasting glucose, 31.2% (48 subjects, 23.9–38.5%) had impaired glucose tolerance (IGT) and 76% (117 subjects, 69.3–82.7%) had abnormal glucose tolerance. Applying the ADA criteria (fasting capillary whole blood only), 33.1% (51 subjects, 25.7–40.5%) had diabetes (a 26% relative reduction) and 11% (17 subjects, 6.1–15.9%) IFG, with 44.1% (68 subjects, 36.3–51.9%) having abnormal glucose metabolism (a 42% relative reduction). If the proposed 1998 WHO criteria were used, the number with diabetes increase to 48% (74 subjects, 40.1–55.9%) a 7.2% increase on the old criteria. 27.9% (43 subjects, 20.8–35%) had IGT, so the number with some degree of abnormal glucose metabolism remains unchanged. Use of the ADA criteria, considering only the fasting glucose as suggested, will result in a significant reduction in the diagnosis of diabetes and those with abnormal glucose metabolism.

Diabet. Med. 16, 343–346 (1999)
Nesidioblastosis, myelodysplastic syndrome and nodular diabetic glomerulosclerosis in an elderlynondiabetic woman: an autopsy report
Authors: Yeh S. ‐P. , Wang J. ‐S. , Wu H. , Yu M. ‐S. , Hsueh E. ‐J. , Wang Y. ‐C.
Published: March 2003

Nesidioblastosis as the cause of hyperinsulinaemic hypoglycaemia in an adult is rare. We report here an additional case of nesidioblastosis, which resulted in fatal hyperinsulinaemic hypoglycaemia in a 72‐year‐old woman with an underlying myelodysplastic syndrome. The diagnosis of nesidioblastosis was established only after post‐mortem examination with a careful exclusion of minute insulinoma. To our surprise, the renal pathology disclosed typical diabetic nodular glomerulosclerosis in the same patient who had no previous history of diabetes mellitus (DM). Nesidioblastosis has been reported to cause ‘reversal’ of Type 1 DM and insulinoma causing ‘reversal’ of Type 2 disease. We therefore hypothesize that our patient might have had an undiagnosed DM in the past, which resulted in the typical diabetic nodular glomerulosclerosis. The nesidioblastosis caused a ‘reversal’ of DM and even the ultimate development of hyperinsulinaemic hypoglycaemia.

Diabet. Med. 16, 437–441 (1999)
Improvement of blood glucose control in Type 1 diabetic patients treated with lispro and multiple NPH injections
Authors: Colombel A. , Murat A. , Krempf M. , Kuchly‐Anton B. , Charbonnel B.
Published: March 2003

Aims To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally.

Methods Twenty‐five C‐peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20–30 min before each meal and NPH at bed‐time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32 ± 1.5%.

Results The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75 ± 0.36 g/l vs. 0.99 ± 0.50, P < 0.01; MODD 0.64 ± 0.26 g/l vs. 0.80 ± 0.40, P < 0.05). There was a nonsignificant reduction in HbA1c with lispro: –0.40 ± 0.86 vs. –0.08 ± 0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53 ± 0.48 g/l vs. 1.82 ± 0.57 g/l, P < 0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%).

Conclusions An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day‐to‐day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.

Diabet. Med. 16, 319–324 (1999)
Diabetes mellitus in the family: perceptions of offspring’s risk
Authors: Pierce M. , Hayworth J. , Warburton F. , Keen H. , Bradley C.
Published: March 2003

Aims The study aimed to explore the beliefs and concerns of people with Type 2 diabetes mellitus (DM) about their children’s risk of developing the disease and the possibilities for prevention.

Methods Questionnaires were posted to all patients with Type 2 DM in four randomly selected general practices in South London. Two hundred and thirteen (73%) responded. The main outcome measures were: estimated risk of Type 2 DM in their offspring; worry about diabetes in their offspring; knowledge about the possibilities for prevention of Type 2 DM and its complications.

Results Of the 159 respondents with children, at least 35% and perhaps as many as 64% underestimated the risk of their offspring developing Type 2 DM; 44% thought it possible to reduce the risk of Type 2 DM and its complications; 28% thought altering diet and 6% taking exercise might be useful preventive strategies; 49% worried about their children developing diabetes.

Conclusions Although risk of Type 2 DM was underestimated for their children and little was known about prevention, about half of the respondents worried about their children developing diabetes. Education and counselling about risk and prevention are needed. This is important in view of growing interest in and opportunities for both the primary and secondary prevention of Type 2 DM.

Diabet. Med. 16, 431–436 (1999)
Effect of metformin on patients with impaired glucose tolerance
Authors: Li C. L. , Pan C. Y. , Lu J. M. , Zhu Y. , Wang J. H. , Deng X. X. , Xia F. C. , Wang H. Z. , Wang H. Y.
Published: March 2003

Aims To evaluate the effect of metformin on glucose metabolism, insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance (IGT).

Methods Seventy subjects with IGT were randomized under double‐blind conditions to receive either placebo (n = 37) or metformin (n = 33) at a dosage of 250 mg three times daily for a duration of 12 months. Glycaemic control, plasma insulin and other biochemical indexes were assessed before and after 3, 6 and 12 months.

Results At 12 months the conversion rate to diabetes was 16.2% in the placebo group compared to 3.0% for the metformin group (P = 0.011). Of subjects treated with metformin for 12 months, 84.9% became normoglycaemic compared to 51.4% of those receiving the placebo. Significant improvements in fasting glucose, glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessments.

Conclusions Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects.
Amniotic fluid insulin levels identify the fetus at risk of neonatal hypoglycaemia
Authors: Fraser R. B. , Bruce C.
Published: March 2003

Aims To investigate the use of amniotic fluid insulin (AFI) as a predictor of neonatal morbidity in the macrosomic newborn of the diabetic mother, in view of the fact that raised AFI levels are a marker for fetal hyperinsulinaemia.

Methods AFI was measured by radioimmunoassay in a group of pregnant diabetic women (n = 63) with normal (n = 41) or accelerated fetal growth (n = 22).

Results Using log transformed data, liquor insulin was found to be significantly higher in pregnant women with Type 1 and Type 2 diabetes mellitus (17.6 mU/l; 95% confidence interval (CI) 11.7–26.4) compared with women with gestational diabetes mellitus (GDM) (8.2 mU/l; 95% CI 4.8–13.8, P = 0.02) or impaired glucose tolerance (IGT) (6.2 mU/l; 95% CI 4.9–8.0, P = 0.0001). In the group with macrosomic fetuses (birth weight > 90th centile for gestational age), there was a significantly higher incidence of elective Caesarean section (CS) and emergency CS (12/22) compared to those with appropriate for gestational age (AGA) fetal weights (birth weight > 10th and < 90th centiles for gestational age) (9/41, P = 0.009). There was no significant correlation between raised AFI and macrosomia except in the Type 1 diabetic women, in whom the AGA group mean was 13.2 mU/l (95% CI 7.4–23.3), and 34.6 mU/l (95% CI 17.5–68.4 P = 0.022) in macrosomia. In the latter group, hypoglycaemia requiring treatment was significantly more common in the macrosomic hyperinsulinaemic neonates (8/13), compared to normoinsulinaemic neonates in the same group (0/9, P = 0.005).

Conclusions Identification of the hyperinsulinaemic fetus before delivery might allow the intensification of maternal insulin therapy leading to a reduction in incidence and severity of diabetic fetopathy. Pregnancy with a normoinsulinaemic fetus could be allowed to continue to the onset of spontaneous labour, which might result in a lower CS rate.
A paper which changed clinical practice (slowly). Jacob Holler on potassium deficiency in diabetic acidosis (1946)
Authors: Tattersall R. B.
Published: March 2003

It is often said that the introduction of insulin into clinical medicine made a ‘dramatic’ difference to the mortality resulting from diabetic coma. This is true in the sense that before 1922 it was almost uniformly fatal, but until the 1950s the mortality in many large hospitals was as high as 30–50%. Often autopsy did not establish a cause of death. Many may have been a result of hypokalaemia, a complication which was not recognized until 1946; in that year in the Journal of the American Medical Association, Jacob Holler described a patient who developed respiratory paralysis 12 h into treatment that, after several hours in an iron lung, was cured by potassium infusion. In the 5 years after Holler’s paper there were many reports of deaths resulting from hypokalaemia, as well as several ‘near misses’, but clinicians were extremely cautious about early replacement probably, as an editorialist in The Lancet suggested, because ‘the frightening effects of intravenous injections of potassium made clinicians reluctant to believe in a lack of potassium as a cause of trouble, except in very rare conditions such as familial periodic paralysis’.

It had been known since 1923 that insulin lowered serum potassium, but this was not of great interest because the symptoms of hypokalaemia were not known. Also, potassium was not an electrolyte with which clinicians were familiar. Until the introduction of flame photometry in 1950, it was only measured in research studies as chemical methods took several hours to complete.
Comparison of vasodilator effects of substance P in human forearm vessels of normoalbuminuric Type 1 diabetic and non‐diabetic subjects
Authors: Meeking D. R. , Allard S. , Munday J. , Chowienczyk P. J. , Shaw K. M. , Cummings M. H.
Published: March 2003

Aims To compare the vasodilatory responses to substance P in human forearm vessels in Type 1 normoalbuminuric diabetic and non‐diabetic subjects.

Methods Forearm blood flow (FBF) was measured using a plethysmography technique in 12 normoalbuminuric Type 1 diabetic subjects (six males, six females) (HbA1C 8.2 ± 0.3% (mean ± sem)) and 12 non‐diabetic healthy control subjects in response to the infusion of the vasodilators substance P (SP), acetylcholine (ACh) and nitroprusside.

Results There was no significant difference in baseline FBF between the two groups (2.80 ± 0.29 ml/min per 100 ml forearm tissue (diabetic group) vs. 2.85 ± 0.37 ml/min per 100 ml (non‐diabetic group), P = 0.45). Infusion of SP was associated with an incremental increase in FBF in the diabetic (0.6, 2 and 6 ng/min – 6.08 ± 1.07, 7.82 ± 1.08 and 9.48 ± 1.14 ml/min per 100 ml, respectively) and the non‐diabetic group (0.6, 2 and 6 ng/min – 5.41 ± 0.80, 6.93 ± 0.96 and 9.25 ± 1.11 ml/min per 100 ml, respectively). Similarly, an incremental rise in FBF was observed during infusion of ACh (diabetic group: 7.5, 15 and 30 μg/min – 7.14 ± 1.22, 8.91 ± 1.40 and 11.67 ± 1.93 ml/min per 100 ml, respectively; non‐diabetic group: 7.5, 15 and 30 μg/min – 5.87 ± 0.81, 7.49 ± 0.96 and 10.74 ± 1.29 ml/min per 100 ml, respectively). When FBF was expressed as percentage change from baseline, there was no significant difference in vasodilatory responses between the two groups for SP (0.6 ng/min, P = 0.21; 2 ng/min, P = 0.19; 6 ng/min, P = 0.19) or ACh (7.5 μg/min, P = 0.20; 15 μg/min, P = 0.20; 30 μg/min, P = 0.35).

Conclusions This study suggests that endothelium‐dependent vasodilatory responses to SP (and ACh) are not impaired in Type 1 diabetic subjects with normal urinary albumin excretion.
Rosiglitazone taken once daily provides effective glycaemic control in patients with Type 2 diabetes mellitus
Authors: Nolan J. J. , Jones N. P. , Patwardhan R. , Deacon L. F.
Published: March 2003

Aims To evaluate the clinical efficacy and safety of rosiglitazone as a once daily treatment for Type 2 diabetes mellitus (DM).

Methods Three hundred and sixty‐nine patients with Type 2 DM (mean age 63 years; mean body mass index (BMI) 29.4 kg/m2) were enrolled in a double‐blind, parallel group, placebo‐controlled, dose‐ranging study. Patients were randomly assigned to receive placebo or rosiglitazone at doses of 4, 8, or 12 mg daily for 8 weeks.

Results At 8 weeks, fasting plasma glucose (FPG) decreased significantly in the rosiglitazone 4 mg, 8 mg, and 12 mg groups (−0.9, −2.0 and −1.7 mmol/l; P = 0.0003, < 0.0001, and < 0.0001, respectively) compared with placebo (+0.4 mmol/l). The improvements in FPG were dose ordered for 4 and 8 mg/day. The 12 mg/day dose produced no additional improvement. There were small decreases in haemoglobin and haematocrit in the rosiglitazone treatment groups. The overall incidence of adverse experiences was similar in all treatment groups, including placebo with no evidence of hypoglycaemia or hepatotoxicity.

Conclusions Rosiglitazone improves glycaemic control when given once daily to treat Type 2 diabetes mellitus and is well tolerated at doses up to and including 12 mg.
Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor‐1α gene mutations: evidence for pharmacogenetics in diabetes
Authors: Pearson E. R. , Liddell W. G. , Shepherd M. , Corrall R. J. , Hattersley A. T.
Published: March 2003

SUMMARY

Introduction  Maturity‐onset diabetes of the young (MODY) is characterized by autosomal dominantly inherited, early‐onset, non‐insulin‐dependent diabetes. Mutations in the hepatocyte nuclear factor (HNF)‐1α gene are the commonest cause of MODY. Individual patients with HNF‐1α mutations have been reported as being unusually sensitive to the hypoglycaemic effects of sulphonylurea therapy. We report three patients, attending a single clinic, with HNF‐1α mutations that show marked hypersensitivity to sulphonylureas.

Case reports  In cases 1 and 2 there were marked changes in HbA1c on cessation (4.4% and 5.8%, respectively) and reintroduction (5.0% and 2.6%) of sulphonylureas. Case 3 had severe hypoglycaemic symptoms on the introduction of sulphonylureas despite poor glycaemic control and was shown with a test dose of 2.5 mg glibenclamide to have symptomatic hypoglycaemia (blood glucose 2 mmol/l) after 4 h despite eating.

Conclusions  HNF‐1α MODY diabetic subjects are more sensitive to sulphonylureas than Type 2 diabetic subjects and this is seen in different families, with different mutations and may continue up to 13 years from diagnosis. This is an example of pharmacogenetics, with the underlying aetiological genetic defect altering the pharmacological response to treatment. The present cases suggest that in HNF‐1α MODY patients: (i) sulphonylureas can dramatically improve glycaemic control and should be considered as initial treatment for patients with poor glycaemic control on an appropriate diet; (ii) hypoglycaemia may complicate the introduction of sulphonylureas and therefore very low doses of short acting sulphonylureas should be used initially; and (iii) cessation of sulphonylureas should be undertaken cautiously as there may be marked deterioration in glycaemic control.

Keywords  genetics, HNF‐1α, MODY, pharmacogenetics, sulphonylurea sensitivity
Different effects of glucose on extracellular and intracellular respiratory burst response in normal human neutrophils activated with the soluble agonist fMet‐Leu‐Phe
Authors: Oldenborg P. ‐A. , Sundqvist I. ‐M. , Sehlin J.
Published: March 2003

SUMMARY

Aims  The study evaluated the effects of glucose concentration on the extracellular and intracellular activation of the respiratory burst in fMet‐Leu‐Phe‐stimulated normal human neutrophils.

Methods  Specific extracellular respiratory burst activity was measured as superoxide dismutase (SOD)‐inhibitable cytochrome c reduction. Intracellular respiratory burst activity was studied using luminol‐enhanced chemiluminescence in the presence of SOD and catalase, to quench extracellular chemiluminescence activity. Myeloperoxidase (MPO) release from activated neutrophils was studied by using the guaiacol technique.

Results  The extracellular respiratory burst following activation with 1 μM fMet‐Leu‐Phe was significantly reduced at 15 and 25 mM d‐glucose (9.5 ± 1.0 and 8.5 ± 0.8 nmol/106 cells and 10 min; P < 0.01 and P < 0.001, respectively) as compared with that at 5 mM glucose (10.3 ± 1.0 nmol/106 cells and 10 min). When specifically studying the intracellular respiratory burst, no difference was found between the responses at 5, 15 or 25 mM glucose. Increasing glucose concentrations also reduced the secretion of MPO from fMet‐Leu‐Phe‐activated neutrophils.

Conclusions  Elevated glucose concentrations inhibit the generation of extracellularly released reactive oxygen metabolites but have no effects on the intracellular respiratory burst in fMet‐Leu‐Phe‐stimulated normal human neutrophils.
A case of hand ulceration in the diabetic foot clinic – a reminder of hand neuropathy in ‘at risk’ patients
Authors: Coppini D. V. , Best C.
Published: March 2003

SUMMARY

Background  A case of hand ulceration in a diabetic patient with known lower extremity complications is presented. Although often asymptomatic, quantitative testing in patients indicates reduced hand sensation in patients with lower extremity neuropathy. Hand neuropathy may occasionally lead to anaesthetic injuries, particularly in certain ‘manual’ occupations, as seen in our patient.

Conclusions   Education on hand care is virtually inexistent in most clinic settings, and our case highlights the need for more awareness on this potentially troublesome complication.
Does dietary protein intake correlate with markers suggestive of early diabetic nephropathy in children and adolescents with Type 1 diabetes mellitus?
Authors: O'hayon B. E. , Cummings E. A. , Daneman D. , Ossip M. G. , Lawson M. L. , Sochett E. B.
Published: March 2003

SUMMARY

Aims  To examine the relationship between dietary protein intake and possible early markers of diabetic nephropathy (creatinine clearance (CrCl), kidney volume and albumin excretion rate (AER)).

Methods  One hundred and forty‐five subjects with diabetes for 5–10 years, divided into three pubertal groups, participated. Kidney volume was measured by ultrasound, and serum creatinine and HbA1c were assayed. Two or three 24‐h urine collections were obtained for albumin, creatinine and urea excretion rates. Dietary protein intake was estimated from urinary urea nitrogen excretion rate. Glomerular filtration rate was estimated by creatinine clearance.

Results  Mean protein intake was 1.22 ± 0.48 g.kg−1.day−1 Protein intake was significantly higher in males than females (P < 0.0001) and highest in pre‐pubertal compared to mid‐pubertal and post‐pubertal subjects (P < 0.001). In multiple regression analysis, protein intake was positively associated with CrCl (P < 0.0001), and male sex (P < 0.0001) and negatively associated with body surface area (P = 0.0013) and age (P = 0.01). Kidney volume and AER were not related to dietary protein intake.

Conclusions  This cross‐sectional study failed to show a significant relationship between dietary protein intake and markers of early nephropathy, other than CrCl. However, a longitudinal, prospective study is required to definitively assess the role of protein intake in the evolution of diabetic nephropathy.
Autonomic neuropathy – a complication less pronounced in patients with Type 1 diabetes mellitus who have lower blood glucose levels
Authors: Reichard P. , Jensen‐Urstad K. , Ericsson M. , Jensen‐Urstad M. , Lindblad L. E.
Published: March 2003

SUMMARY

Aims  Autonomic neuropathy is a serious diabetic complication, probably contributing to the death of many young people with Type 1 diabetes mellitus. It is often not diagnosed.

Methods  Patients with Type 1 diabetes from the Stockholm Diabetes Intervention Study were investigated with power spectral analysis (n = 88), heart rate and blood pressure reactions to tilting (n = 66), and heart rate variability during deep breathing (n = 70) a mean of 11.4 years after randomization to intensified conventional treatment (ICT) or standard treatment (ST), the treatment groups similar with regard to age, duration of diabetes and metabolic control at baseline (HbA1c 9.4 (1.3)%, mean (sd)). Blood glucose levels (mean of 29 HbA1c values) during the 10 years were lower in the patients from the ICT group (7.2 (0.6) vs. 8.3 (1.0)%, P = 0.001).

Results  Heart rate variability (HRV) in the high frequency range (P = 0.034), the expiration–inspiration ratio (P = 0.020), and the brake index during tilt (P = 0.044) were lower in the ST group, indicating more pronounced parasympathetic insufficiency. Systolic blood pressure fell by 10 (16) mmHg in the ST group, and by 2.5 (15) mmHg in the ICT group 8 min after rising from the supine to a 70° upright position (P = 0.034). A decreased autonomic function was associated with age and higher HbA1c.

Conclusion  Better autonomic nerve function is associated with lower HbA1c and lower age which were both the same in the intensively and the conventionally treatment groups at baseline. After a mean of 11.4 years autonomic function was better in the intensively treated group.
Circulating plasma vascular endothelial growth factor and microvascular complications of Type 1 diabetes mellitus: the influence of ACE inhibition
Authors: Chaturvedi N. , Fuller J. H. , Pokras F. , Rottiers R. , Papazoglou N. , Aiello L. P. ,   the Euclid Study Group
Published: March 2003

SUMMARY

Aims  To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin‐converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF.

Methods  Samples (299/354 of those with retinal photographs) from the EUCLID placebo‐controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non‐hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated.

Results  No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0–27.9) pg/ml in those without retinopathy, 12.9 (6.0–38.9) pg/ml in those with non‐proliferative retinopathy, and 16.1 (8.1–33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER.

Conclusions  Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.
Child and parental mental ability and glycaemic control in children with Type 1 diabetes
Authors: Ross L. A. , Frier B. M. , Kelnar C. J. H. , Deary I. J.
Published: March 2003

SUMMARY

Aims  Many psycho‐social factors can affect the glycaemic control of children with Type 1 diabetes, but the influence of the intelligence of the child and their parents has not been reported.

Methods  Seventy‐eight children and adolescents with Type 1 diabetes and their mothers performed standardized tests to assess psychometric intelligence. The children were aged (median (range)) 12.0 (5–17) years with duration of diabetes 5.0 (1.0–13.0) years and required an insulin dose of (mean ± sd) 1.0 ± 0.3 U/kg per day. The children completed the Wide Range Achievement Test 3 reading test (WRAT3) and Raven's Standard Progressive Matrices (RSPM). A mean annual HbA1c was calculated for each subject (8.6 ± 1.4%). The mothers performed the National Adult Reading Test (NART) and provided details of the occupation of the main wage‐earner in the family from which social class (SC) was derived.

Results  The HbA1c of the child correlated with their age (r = 0.26, P = 0.02), SC (Kendall's rank correlation, τ = 0.17, P = 0.03) and with the NART error score of their mother (r = 0.28, P = 0.01), but no correlation was observed with the child's WRAT3 or RSPM score. Stepwise regression revealed that age and NART error score were the strongest independent determinants of glycaemic control (total adjusted r2 = 0.117).

Conclusions  Parental intelligence appears to have a significant influence on the glycaemic control of a child with Type 1 diabetes, accounting for 7.6% of the reliable variance in HbA1c.
Reversible amnesia in a Type 1 diabetic patient and bilateral hippocampal lesions on magnetic resonance imaging (MRI)
Authors: Holemans X. , Dupuis M. , Misson N. , Vanderijst J.‐F.
Published: March 2003

Aims  Intensive insulin therapy of Type 1 diabetes limits its chronic complications, but is associated with an increased risk of severe hypoglycaemia and its neuroglycopenic consequences.

Methods  Case report.

Results  A 24‐year‐old male with 15 years' history of Type 1 diabetes, who was missing for 48 h, was found at home in ketoacidosis coma. Intensive care permitted a rapid improvement revealing an unexpected severe anterograde amnesia, confirmed by neuropsychological testing. MRI performed 4 days after admission showed abnormal bilateral hyperintensity signals on T2‐weighted images in the hippocampus. Three months later, the patient had nearly completely recovered and resumed work. MR images and neuropsychological testing returned to normal.

Conclusions  The most likely course of events favours an initial prolonged hypoglycaemic coma following insulin overdose. The hippocampal injury may be a result of hypoglycaemia. Neuropsychological testing and MRI abnormalities were completely reversible. This case underlines the potential risks of intensive insulin therapy.

Diabet. Med. 18, 761–763 (2001)
Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing
Authors: Penfornis A. , Zimmermann C. , Boumal D. , Sabbah A. , Meneveau N. , Gaultier‐Bourgeois S. , Bassand J. P. , Bernard Y.
Published: March 2003

Aims  Silent myocardial ischaemia is frequent in diabetic patients. The aim of this study was to compare the efficacy of thallium‐201 single‐photon emission computed tomography (201Tl SPECT) coupled with exercise stress testing (EST), and dobutamine stress echocardiography (DSE) in the detection of asymptomatic coronary artery disease.

Methods  Fifty‐six asymptomatic diabetic patients, with a known duration of diabetes > 15 years for Type 1 and > 5 years for Type 2, having at least three added risk factors, but without rest ECG abnormalities, were enrolled in this prospective study. All of them were submitted to DSE with a maximum infusion rate of 40 µg/kg per min dobutamine ± i.v. atropine, and to 201Tl SPECT coupled with EST. Coronary angiography was performed if at least one test was abnormal.

Results  Diabetic patients were 37 males and 19 females, aged mean (sd) 60 ± 10 years, 10 Type 1 and 46 Type 2, with a known duration of disease of mean (sd) 17 ± 9 years. Feasibility of DSE was 91%. No serious complication occurred during the test. Coronary angiography was performed in 26 patients (47%); 17 were abnormal (30% of the whole group): six patients had a one‐vessel, six a two‐vessel and five a three‐vessel disease. Predictive positive value was 69% for DSE, 75% for 201Tl SPECT and 60% for EST. DSE was falsely negative in four cases vs. eight for 201Tl SPECT and nine for EST.

Conclusions  Asymptomatic coronary disease is common in diabetes associated with other risk factors. DSE appears useful in its detection and a good alternative to 201Tl SPECT.

Diabet. Med. 18, 900–905 (2001)
Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus?
Authors: White K. E. , Pinel N. , Cordonnier D. J. , Bilous R. W. ,   for the Diabiopsies Group
Published: March 2003

Aims  To examine the effect of ACE inhibition on glomerular structure in Type 2 diabetic patients with nephropathy.

Methods  Twenty‐two patients were randomized to receive either perindopril (PE) or placebo (PO) and biopsied at baseline and after 2 years. Nineteen patients completed the study and data on interstitial changes, examined by light microscopy, have already been published. Only 11 patients (five PE, six PO) had sufficient tissue at baseline and follow‐up to provide material for detailed electron microscopic examination.

Results  At baseline, mean ± sd age (PE vs. PO) was 48 ± 12 vs. 45 ± 7 years; creatinine clearance 116 ± 24 vs. 128 ± 68 ml/min; median (range) proteinuria 0.7 (0.1–1.0) vs. 0.5 (0.07–3.9) g/24 h (P = NS for all). This cohort of 11 patients showed the same interstitial changes as the whole group. Between‐group analysis showed that the change in interstitial volume fraction was significantly greater in the PO compared with PE group (0.10 ± 0.07 vs. −0.001 ± 0.04, P = 0.020). There were no significant changes in proteinuria or glomerular structural parameters (mesangial volume fraction PO 0.40 ± 0.17 to 0.42 ± 0.21; PE 0.29 ± 0.08 to 0.28 ± 0.14) in either treatment group.

Conclusions  Interstitial changes appear to be more sensitive to ACE inhibition than glomerulopathy. Larger patient groups and longer treatment periods are necessary in order to detect any possible impact of ACE inhibition on the glomerular changes in Type 2 diabetes mellitus.

Diabet. Med. 18, 933–936 (2001)
Use of oral fluorescein angiography in the diagnosis of macular oedema within a diabetic retinopathy screening programme
Authors: Razvi F. M. , Kritzinger E. E. , Tsaloumas M. D. , Ryder R. E. J.
Published: March 2003

Aims  To assess if oral fluorescein angiography (OFA) is a suitable screening method to detect macular oedema in diabetic retinopathy.

Methods  Eighty‐four diabetic patients were included in the study. They were from a consecutive series of patients attending the diabetic eye‐screening clinic, with retinopathy at the macula requiring ophthalmology assessment. All patients were subsequently examined in the eye hospital, by ophthalmologist slit lamp biomicroscopy assessment as the gold standard, followed by oral fluorescein angiography.

Results  This study indicates a sensitivity of 92% and specificity of 81%. Only 4.8% of patients developed a minor reaction to oral fluorescein; 84.5% of images were of good quality.

Conclusions  Oral fluorescein angiography is an efficient and highly sensitive tool for the detection of macular oedema. It can be used as an adjunct in the diabetic screening service to identify patients with oedema within a disc diameter of the macula. Ultimately it will ensure that only necessary and smaller numbers of patients are referred to ophthalmologists.

Diabet. Med. 18, 1003–1006 (2001)
Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study
Authors: Donnan P. T. , MacDonald T. M. , Morris A. D.
Published: March 2003

Aims To evaluate the patterns and predictors of adherence in all patients with Type 2 diabetes in the community receiving treatment with a single oral hypoglycaemic drug. In particular, to test the hypothesis that one tablet per day is associated with better adherence than more than one.

Methods The study design was a retrospective cohort study set in the Tayside region of Scotland (population approx. 400 000). Participants were residents of Tayside from 1 January 1993 until 31 December 1995 with at least 12 months of prescriptions of oral hypoglycaemic drugs (OHDs). The main outcome measures were adherence indices for sulphonylureas and metformin separately, adjusting for prescribing while hospitalized.

Results Of the total 2920 subjects identified, adequate adherence (≥ 90%) was found in 31% of those prescribed sulphonylureas alone (n = 1329, median adherence = 300 days per year), and in 34% of those prescribed metformin alone (n = 528, median = 302 days per year). There were significant linear trends of poorer adherence with each increase in the daily number of tablets taken (p = 0.001) and increase in co‐medication (p = 0.0001) for sulphonylureas alone after adjustment for other factors.

Conclusions In the community only one in three with Type 2 diabetes had adequate adherence to OHDs. One tablet per day administration was associated with greater adherence than multiple tablets. Poor adherence is a major obstacle to the benefit of complex drug regimens in the treatment of Type 2 diabetes.
Trends in the incidence of childhood diabetes in south Asians and other children in Bradford, UK
Authors: Feltbower R. G. , Bodansky H. J. , McKinney P. A. , Houghton J. , Stephenson C. R. , Haigh D.
Published: March 2003

Aims To investigate incidence rates and time trends, over 21 years, of Type 1 diabetes in a migrant population of south Asian children in Bradford, UK.

Methods Children (0–14 years) living in the city of Bradford and diagnosed with Type 1 diabetes were selected from a population‐based region‐wide register. Between 1978 and 1998, 289 new‐onset cases were registered and classified as south Asian (Indian, Pakistani, Bangladeshi) or not, based on their full name using two different computer algorithms and visual inspection.

Results Sixty‐six children (22.8%) were designated as south Asian with 223 (77.2%) remaining. The overall age–sex standardized incidence for south Asian and non‐south Asian children was 13.0 per 100 000 person years (95% confidence interval 9.9–16.2) and 12.9 (11.2–14.6), respectively. Rates were similar for south Asians at all ages, whereas for the mainly Caucasian children incidence differed significantly by age group (P < 0.001). An average annual increase in incidence of 4.3% (P = 0.001) was seen for all children compared with 6.5% in south Asians (P = 0.002) and 2.4% (P = 0.128) in non‐south Asians.

Conclusions Children in south Asia have a low incidence of Type 1 diabetes but migrants to the UK have similar overall rates to the indigenous population. However, a more steeply rising incidence is seen in the south Asian population, and our data suggest that incidence in this group may eventually outstrip that of the non‐south Asians. Genetic factors are unlikely to explain such a rapid change, implying an influence of environmental factors in disease aetiology. The similarity in rates by age group in the south Asian population is notable.
Prognosis following first acute myocardial infarction in Type 2 diabetes: a comparative population study
Authors: Donnan P. T. , Boyle D. I. R. , Broomhall J. , Hunter K. , MacDonald T. M. , Newton R. W. , Morris A. D. ,   for the DARTS/MEMO Collaboration
Published: March 2003

AimsTo estimate the incidence of death and macrovascular complications after a first myocardial infarction for patients with Type 2 diabetes.

Research designIn a retrospective, incidence cohort study in the Tayside Region of Scotland we studied all patients hospitalized with a diagnosis of first acute myocardial infarction from 1 April 1993 to 31 December 1994. The primary endpoint was time to death. Secondary endpoints were 2‐year incidence of hospital admission for angina, myocardial infarction, stroke, heart failure, coronary angiography, coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA).

ResultsThe 147 patients with Type 2 diabetes had significantly worse survival with an increase in relative hazard of 67% compared with non‐diabetic patients. After adjustment for age, sex, smoking status, prior heart failure, prior angina, delay to hospitalization, site of infarction, drug therapy with aspirin, β‐blockers, streptokinase and hyperlipidaemia and treated hypertension, Type 2 diabetes was still associated with a 40% higher death rate compared with people without diabetes (P < 0.05) There was no significant difference in death rates in those aged over 70 years, but an indication of a trend in younger individuals with a four‐fold increase in death rate in those with diabetes aged < 60 years, compared with a rate ratio of 2.6 in those with diabetes aged 61–70 years.

ConclusionsAmong hospitalized patients with first acute myocardial infarction, Type 2 diabetes mellitus is consistently associated with increased mortality and increased hospital admission for heart failure. The estimated 4‐year survival rate is only 50%. Our results indicate that younger subjects with Type 2 diabetes and acute myocardial infarction are a high‐risk group deserving of special study, and support the argument for aggressive targeting of coronary risk factors among patients with Type 2 diabetes.
Less severe hypoglycaemia, better metabolic control, and improved quality of life in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy; an observational study of 100 consecutive patients followed for a mean of 2 years
Authors: Linkeschova R. , Raoul M. , Bott U. , Berger M. , Spraul M.
Published: March 2003

Aims To compare glycaemic control, occurrence of acute complications, and diabetes‐specific quality of life in Type 1 diabetic patients (on intensified conventional insulin treatment (ICT)) before and after initiation of CSII.

Methods One hundred and three patients (58 women) started CSII between October 1995 and April 1999 in our department. The indication for CSII was optimization of metabolic control and improvement of flexibility of life style (OF group) in 60 patients (58%), and prevention of severe hypoglycaemia (HY group) in 43 patients. Mean age at initiation of CSII was 33 ± 11 years (OF 33 ± 10, HY 33 ± 11 (mean ± sd)), diabetes duration 18 ± 9 years (OF 16 ± 9, HY 20 ± 9). Three patients stopped CSII, mean duration of CSII of the remaining 100 patients was 1.8 ± 1.2 years. The occurrence of hypoglycaemia, ketoacidosis and skin abscesses was assessed retrospectively for the 12 months before starting CSII, and recorded continuously during CSII. Quality of life was assessed with a validated, diabetes‐specific questionnaire before and after CSII in 50 patients.

Results The incidence of serious hypoglycaemia (any external help) was reduced from 1.23 (OF 0.0; HY 2.93) during ICT to 0.29 cases/patient per year (OF 0.09; HY 0.55) during CSII. The incidence of severe hypoglycaemia (SH) (treated with i.v. glucose or glucagon injection) fell from 0.70 (OF 0.0; SH 1.67) during ICT to 0.06 cases/patient per year (OF 0.02; HY 0.12) during CSII. HbA1c improved from 7.7 ± 1.1% to 7.2 ± 1.0% (P < 0.001) (OF 7.8% vs. 7.2%; HY 7.6% vs. 7.2%). During CSII the incidence of abscesses was 0.11 and of ketoacidosis 0.01 cases/patient per year. Quality of life assessments showed significant improvement in all parameters during CSII.

Conclusions In our cohort of Type 1 diabetic patients, we observed a substantial decrease of hypoglycaemia along with a significant fall of HbA1c. Quality of life on CSII was improved when compared with ICT.
Serum fructosamine as a marker of 5‐year risk of developing diabetes mellitus in patients exhibiting stress hyperglycaemia
Authors: Wahid S. T. , Sultan J. , Handley G. , Saeed B. O. , Weaver J. U. , Robinson A. C. J.
Published: March 2003

Aims We examined whether the level of random serum glucose (RSG) in subjects exhibiting stress hyperglycaemia is a useful marker of the future risk of developing diabetes mellitus (DM), and whether serum fructosamine is of any additional value.

Methods All non‐diabetic adults attending Accident and Emergency in 1994–1995, who had venesection, were studied. Serum fructosamine and RSG were routinely measured in all such patients. Using the laboratory biochemistry database the number of subjects with stress hyperglycaemia (RSG > 11.1 mmol/l) was determined, and their corresponding fructosamine values were recorded. The number of subjects who developed DM over the following 5 years was determined.

Results Three hundred and seventeen patients had stress hyperglycaemia, and follow‐up data were available on 224 patients. Of these patients, 63 (28%) had developed DM over the 5 years follow‐up period. RSG and fructosamine levels at baseline of patients subsequently developing DM were (mean ± sd (range)) 16.7 ± 7.0 (11.2–55.0) mmol/l and 3.3 ± 0.6 (1.3–4.5) mmol/l, respectively. The patients who did not develop DM had a similar baseline RSG, 15.9 ± 3.3 (11.2–30.6) mmol/l; P = 0.170, but lower baseline fructosamine, 2.4 ± 0.4 (1.6–3.8) mmol/l; P < 0.001. Receiver‐operating characteristics showed that a serum fructosamine ≥ 2.8 mmol/l was a useful marker of the future risk of DM (75% sensitivity, 74% specificity, 53% positive and 88% negative predictive power).

Conclusions The level of RSG in stress hyperglycaemia does not predict the future development of DM. Raised serum fructosamine is a more useful marker of future DM risk than RSG alone. Further prospective studies are needed.
Changes in treatment after the start of oral hypoglycaemic therapy in Type 2 diabetes: a population‐based study
Authors: Donnan P. T. , Steinke D. T. , Newton R. W. , Morris A. D. ,   for the DARTS/MEMO Collaboration
Published: March 2003

AimsTo determine the changes in oral hypoglycaemic therapy and the time to incidence of insulin therapy in people with Type 2 diabetes.

MethodsA retrospective incidence cohort was constructed of 1305 subjects with Type 2 diabetes, who obtained a first prescription for oral hypoglycaemic medication between 1 July 1993 and 31 December 1994 in Tayside, Scotland. The primary endpoint of changes in oral hypoglycaemic therapy and time to insulin was determined up to the end of the follow‐up, on 31 December 1995.

ResultsOverall, 9.4% of subjects switched to insulin, while 11% of those initially on sulphonylurea, and 6% of those initially on metformin switched to insulin therapy. Approximately three‐quarters (72%) remained on the same class of drug throughout the study period (median follow‐up 588 days). Only 9% died during the follow‐up and this did not differ appreciably by drug group. Males were more likely to switch to insulin compared with females (10.3% vs. 8.5%), and those who switched were slightly younger with a mean age of 58 years compared with a mean age of 60 years of those who did not switch. The median time of switching to insulin was 186 days or approximately 6 months for this cohort, giving a rate of switching to insulin of 5.84% per year. Poorer glycaemic control (HBA1c) and low body mass index (BMI) were associated with switching to insulin.

ConclusionsFollowing initial therapy with oral hypoglycaemic medication in the population, switching to insulin occurred at a rate of 5.84% per year. Switching to insulin was associated with being younger, male, having low BMI and higher HbA1c.

Diabet. Med. 19, 606–610 (2002)