bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications
Authors: Chiarelli F. , Spagnoli A. , Basciani F. , Tumini S. , Mezzetti A. , Cipollone F. , Cuccurullo F. , Morgese G. , Verrotti A.
Published: March 2003

SUMMARY

Aims  To evaluate serum levels of vascular endothelial growth factor (VEGF) in a large group of children, adolescents and young adults with Type 1 diabetes mellitus to investigate whether increased VEGF concentrations are associated with long‐term glycaemic control and microvascular complications.

Methods  The study involved 196 patients with Type 1 diabetes mellitus (age range 2–24 years, onset of diabetes before the age of 12 years, duration of disease longer than 2 years), without clinical and laboratory signs of microvascular complications; they were divided into three groups (group 1 –n = 37, age < 6 years; group 2 –n = 71, age 6–12 years; group 3 –n = 88–age > 12 years). Fifty‐three adolescents and young adults (age 16.1–29.7) with different grades of diabetic retinopathy and microalbuminuria were also selected (group 4). A total of 223 healthy controls were matched for age and sex with each group of patients with diabetes mellitus.

Results  VEGF serum levels were significantly increased in pre‐school and pre‐pubertal children with diabetes as well as in pubertal patients compared to controls. VEGF concentrations were markedly increased in adolescents and young adults with microvascular complications compared with both healthy controls and diabetic patients without retinopathy or nephropathy. Multivariate analysis showed that elevation of VEGF in serum was an independent correlate of complications. One‐year mean HbA1c values were significantly correlated with VEGF concentrations (r = 0.372; P < 0.01). Children with HbA1c levels greater than 10% had significantly higher VEGF concentrations when compared with matched patients whose HbAlc levels were lower than 10%. In poorly controlled diabetic children (HbA1c > 10%), long‐term (2 years) improvement of glycaemic control (aiming at HbA1c < 7%) resulted in a significant reduction of VEGF levels.

Conclusions  VEGF serum concentrations are increased in prepubertal and pubertal children with diabetes. Glycaemic control influences VEGF serum levels. Severity of microvascular complications is associated with marked increase of VEGF concentrations in the serum of these patients.
The glycaemic index of a range of gluten‐free foods
Authors: Packer S. C. , Dornhorst A. , Frost G. S.
Published: March 2003

SUMMARY

Aims  The number of people with both diabetes and coeliac disease is increasing. This study examined the effect of gluten‐free, as opposed to gluten‐replete carbohydrate containing foods, on post‐prandial blood glucose concentrations.

Methods  The glycaemic index of six commonly used gluten‐free carbohydrates are reported and compared with published figures for similar non‐gluten‐free products.

Results  The results indicate that the glycaemic index of gluten‐free and gluten containing foods are similar.

Conclusions  The inclusion of gluten‐free foods in the diet of diabetic individuals with coeliac disease should not compromise glycaemic control.
The Child Health Questionnaire in children with diabetes: cross‐sectional survey of parent and adolescent‐reported functional health status
Authors: Wake M. , Hesketh K. , Cameron F.
Published: March 2003

SUMMARY

Aims  To study parent and adolescent‐reported physical, psychosocial and family wellbeing in children aged 5–18 years with diabetes.

Methods  Subjects: 5–18‐year‐olds attending a diabetes clinic at a tertiary children's hospital. Measures: (1) Child Health Questionnaire (CHQ) PF‐50, a functional heath status measure for children aged 5–18 years (parents); (2) CHQ CF‐80, a similar self‐report measure (adolescents aged 12–18 years); (3) 11 study‐designed questions related to diabetes‐specific concerns (parents); (4) global ratings of physical and psychosocial health (clinicians); (5) HbA1c level (all subjects). CHQ data were compared with Australian normative data collected six months earlier.

Results  Reports were obtained from 128 parents and 71 adolescents (90 and 92% response). The CHQ demonstrated good psychometric properties in this sample of children with diabetes. Parents reported children with diabetes to have generally poorer health than children in the normative sample, especially on psychosocial and parent/family scales. Psychosocial health was markedly lower in 5–11‐year‐olds with HbA1c > 8.8%, but not in 12–18‐year‐olds. Presence of diabetes‐related symptoms and concerns correlated with lower physical and psychosocial functioning. Parents and clinicians concurred in their ratings of health for 12–18‐year‐olds but not 5–11‐year‐olds. Adolescents reported their own health similarly to adolescents in the normative sample.

Conclusions  Parents report children aged 5–18 years with diabetes to have poorer health than children in the normative sample across all domains. Clinicians may underrate the impact of diabetes for younger children, with possible therapeutic implications. In providing an overall description of health, instruments like the CHQ may add another dimension to the care of children with diabetes and can feasibly be used within clinical settings.
Lipid hydroperoxide and markers of renal disease susceptibility in African‐Caribbean and Caucasian patients with Type 2 diabetes mellitus
Authors: Mehrotra S. , Ling K. L. E. , Bekele Y. , Gerbino E. , Earle K. A.
Published: March 2003

SUMMARY

Aims  The reasons for the increased incidence of diabetic nephropathy in African‐Caribbean compared with Caucasian subjects are poorly understood. Increased oxidative stress is linked to the development of endothelial dysfunction and histological abnormalities associated with diabetic renal disease. Therefore, it was assessed whether a marker of oxidative stress, lipid hydroperoxide (LOOH) and endothelial damage, von Willebrand factor (vWF) varied according to ethnic origin in the presence or absence of early diabetic nephropathy.

Methods  Eighty‐eight patients with Type 2 diabetes mellitus of African‐Caribbean or Caucasian origin without a history of cardiovascular disease or clinical proteinuria were studied. Patients were classified as having microalbuminuria or normal albumin excretion. Fasting plasma vWF and LOOH were measured by an inhouse enzyme‐linked immunoassay and ferrous oxidation with xylenol orange (FOX) assay, respectively. The relationship of LOOH to urinary albumin status, the metabolic disturbances of diabetes, blood pressure and ethnic origin were assessed using multivariate analysis.

Results  Compared with Caucasian patients those of African‐Caribbean origin had higher systolic blood pressure and HDL‐cholesterol (157.8 ± 17.0 vs. 147.8 ± 24.4, P = 0.041 and 1.6 ± 0.4 vs. 1.3 ± 0.5, P = 0.018) but lower total triglycerides (1.3 ± 0.8 vs. 1.9 ± 1.1, P = 0.008). LOOH was significantly higher in the African‐Caribbean patients compared with Caucasians (5.98 ± 2.49 vs. 4.49 ± 2.19, P = 0.006). vWF tended to be higher in microalbuminuric patients but showed no variation with ethnicity. In logistic regression analysis, LOOH was the only independent predictor of a raised albumin excretion rate (P = 0.008). In multiple regression analysis, African‐Caribbean ethnicity (P = 0.020) HDL‐cholesterol (P = 0.036), total triglycerides (P = 0.002) and a raised albumin excretion rate (P = 0.002) were independent predictors of LOOH.

Conclusions  In this group of Type 2 diabetic patients an increase in LOOH is associated with abnormal urinary albumin excretion. African‐Caribbean origin was a determinant of LOOH independently of microalbuminuria. It is postulated that increased oxidative stress is of pathophysiological significance in accelerating the development of renal disease in African‐Caribbean patients.
Squamous cell carcinoma developing in necrobiosis lipoidica
Authors: Imtiaz K. E. , Khaleeli A. A.
Published: March 2003

We describe a case of squamous cell carcinoma arising in long‐standing necrobiosis lipoidica in a type 1 female diabetic patient. The tumour and the skin lesion were successfully excised and repaired with full thickness skin graft. The development of squamous cell carcinoma in association with this skin disorder is rare (only four cases reported in literature since 1966), but should be considered in chronic, non‐healing and recalcitrant ulcers developing within areas of necrobiosis lipoidica.
Glycated haemoglobin assays. Approaches to standardization of results
Authors: Stott A. , Casson I. F. , Higgins G. J.
Published: March 2003

SUMMARY

Aims  To compare different approaches to DCCT standardization of glycated haemoglobin (HbA1c) results.

Methods  In the first part of the study seven laboratories in the Mersey area participated, using a variety of methods of measurement. The approaches used were the Standardization Initiative for Glycated Haemoglobin Scheme (SIGH) using fresh blood samples and the Wales External Quality Assurance Scheme (WEQAS) using both fresh and lyophilized blood samples. Additional studies performed in the Royal Liverpool University Hospital (RLUH) laboratory involved: (i) re‐calibration of the HPLC analyser using lyophilized blood samples supplied by the manufacturer and (ii) the use of fresh blood samples from the UK National External Quality Assurance Scheme (UKNEQAS).

Results  Inter‐laboratory analytical coefficients of variation following DCCT alignment showed little change. The effect on percentage bias was more marked and was independent of the level of HbA1c. Comparing DCCT‐aligned HbA1c results from 3902 diabetic patients attending the RLUH, indicated that there was a statistically significant difference (P < 0.0001) between the corrected results produced by the five schemes. The effect of DCCT alignment on reported HbA1c values using the different approaches was variable resulting in an apparent increase in the number of diabetic patients with poor glycaemic control (HbA1c values > 7.0%) in all cases.

Conclusion  The method of HbA1c standardization used determines the degree of correction required and a consensus approach is recommended. Implementation will assist extrapolation from research‐based evidence to local practice. Associated changes to patient management must come under the jurisdiction of the physicians responsible for the diabetic service.
Sodium carboxyl‐methyl‐cellulose dressings in the management of deep ulcerations of diabetic foot
Authors: Piaggesi A. , Baccetti F. , Rizzo L. , Romanelli M. , Navalesi R. , Benzi L.
Published: March 2003

SUMMARY

Aims To test the safety and effectiveness of carboxyl‐methyl‐cellulose dressing (AquacelTM; ConvaTec, UK) in the management of deep diabetic foot ulcers, a group of consecutive out‐patients attending the foot clinic of the Department of Metabolic Diseases was studied.

Methods Patients were selected according to the following inclusion criteria: a foot ulcer deeper than 1 cm for > 3 weeks, good peripheral blood supply (palpable peripheral pulses or ABPI > 0.9). Exclusion criteria were as follows: active infection, as evident from clinical signs (purulent discharge, redness, swelling, tenderness) and confirmed by culture exams, plasma creatinine > 2 mg/dl, recent episodes of ketoacidosis, malignancies, and any therapy or pathology which might interfere with the healing process. Twenty patients were enrolled in the study and having obtained their informed consent, their lesions were surgically debrided with the complete elimination of all necrotic tissue and debris up to the bleeding healthy tissue; then ulcers were staged and measured, and patients were randomly assigned to two different treatment groups. Patients in group A were dressed with saline‐moistened gauze, while patients in group B were dressed with AquacelTMaccording to the manufacturer's instructions. All patients in both groups received special post‐operative shoes (Podiabetes; Zeno Buratto, Treviso, Italy) and crutches until complete re‐epithelialization. Ulcers were all left to heal by secondary intent. After 8 weeks patients were blindly evaluated for: the rate of reduction of lesional volume (RLV), rate of granulation tissue (GT), number of infective complications (IC). Intralesional (ILTC) and perilesional (PLTC) temperatures were also recorded with a thermocouple surface digital thermometer, and the difference between the two values (ΔTC) was calculated. Healing time (HT, days), was then compared between the two groups. Data were compared by analysis of variance (anova), linear regression, Kaplan–Meier survival analysis and Fisher's exact test.

Results HT was significantly shorter in Group B than in Group A (P < 0.001). RLV was significantly (P < 0.01) higher in Group B patients compared with Group A, as well as GT (P < 0.05). IC were in 1/10 Group B and in 3/10 Group A (P = 0.582). In addition, both ILTC and ΔTC were higher in Group B compared with Group A ones (P < 0.01).

Conclusions Carboxyl‐methyl‐cellulose dressings were shown to be safe, effective and well tolerated in the management of non‐ischaemic, non‐infected deep diabetic foot ulcers.
Assessment of blood pressure in patients with Type 2 diabetes: comparison between home blood pressure monitoring, clinic blood pressure measurement and 24‐h ambulatory blood pressure monitoring
Authors: Masding M. G. , Jones J. R. , Bartley E. , Sandeman D. D.
Published: March 2003

Aims  To compare a home blood pressure (BP) monitoring device and clinic BP measurement with 24‐h ambulatory BP monitoring in patients with Type 2 diabetes mellitus (DM).

Methods  Fifty‐five patients with type 2 DM had BP measured at three consecutive visits to the DM clinic by nurses using a stethoscope and mercury sphygmomanometer (CBP). Twenty‐four‐hour ambulatory BP was measured using a Spacelabs 90207 automatic cuff‐oscillometric device (ABPM). Subjects were then instructed in how to use a Boots HEM 732B semiautomatic cuff‐oscillometric home BP monitoring device and measured BP at home on three specified occasions on each of 4 consecutive days at varying times (HBPM).

Results  Correlations between HBPM and ABPM were r = 0.88, P < 0.001 for systolic BP and r = 0.76, P < 0.001 for diastolic BP, with correlations between CBP and ABPM being systolic r = 0.59, P < 0.001, diastolic r = 0.47, P < 0.001. HBPM agreed with ABPM more closely compared with CBP (CBP +10.9/+3.8 (95% confidence intervals (CI) 6.9, 14.8/1.6, 6.1) vs. HBPM +8.2/+3.7 (95% CI 6.0, 10.3/2.0, 5.4)). The sensitivity, specificity and positive predictive value of HBPM in detecting hypertension were 100%, 79% and 90%, respectively, compared with CBP (85%, 46% and 58%, respectively).

Conclusions  In patients with Type 2 DM, home BP monitoring is superior to clinic BP measurement, when compared with 24‐h ambulatory BP, and allows better detection of hypertension. It would be a rational addition to the annual review process.

Diabet. Med. 18, 431–437 (2001)
Metabolic effects of metformin in patients with impaired glucose tolerance
Authors: Lehtovirta M. , Forsén B. , Gullström M. , Häggblom M. , Eriksson J. G. , Taskinen M.‐R. , Groop L.
Published: March 2003

Aims
 
To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT).

Methods
 
Forty first‐degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months.

Results
 
Metformin treatment resulted in a 20% improvement in insulin‐stimulated glucose metabolism (from 28.7 ± 13 to 34.4 ± 10.7 µmol/kg fat‐free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 ± 3.6 to 19.1 ± 4.4 µmol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months.

Conclusions
 
Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality.

Diabet. Med. 18, 578–583 (2001)
Peripheral blood level alterations of TIMP‐1, MMP‐2 and MMP‐9 in patients with Type 1 diabetes
Authors: Maxwell P. R. , Timms P. M. , Chandran S. , Gordon D.
Published: March 2003

Aim  To determine the plasma levels of enzymes and inhibitors involved in extracellular matrix turnover in patients with Type 1 diabetes with normal renal function.

Methods  Plasma levels of matrix metalloproteinases 2 and 9 (MMP‐2, MMP‐9) and tissue inhibitor of metalloproteinase 1 (TIMP‐1) were measured in 43 Type 1 diabetic subjects and age‐ and sex‐matched controls.

Results  No significant difference in plasma MMP‐2 between diabetic patients and controls was observed. MMP‐9 was detected in the plasma of 15 diabetic patients (35%), but undetectable in all control subjects (P < 0.015). Plasma TIMP‐1 concentrations were significantly elevated (P < 0.001) in diabetic patients compared to controls. There was no correlation observed between MMP‐2, MMP‐9 and TIMP‐1 and similarly between MMP‐2, MMP‐9 and TIMP‐1 and age, duration of diabetes, blood pressure and glycated haemoglobin (HbA1c).

Conclusions  This study has demonstrated alterations in several plasma extracellular matrix modulators in the absence of significant vascular disease.

Diabet. Med. 18, 777–780 (2001)
Abrupt onset of diabetes during interferon‐alpha therapy in patients with chronic hepatitis C
Authors: Recasens M. , Aguilera E. , Ampurdanés S. , Sánchez Tapias J. M. , Simó O. , Casamitjana R. , Conget I.
Published: March 2003

Introduction Interferon‐alpha (IFN‐α) is now widely used in the treatment of chronic hepatitis C. Few patients have been reported as developing impaired glucose tolerance or diabetes mellitus (DM) using this therapy. The explanation for the development of DM in chronic hepatitis C treated with IFN‐α is unclear. We report two patients who developed an abrupt onset of diabetes during IFN‐α for chronic hepatitis C.

Case reports  Two male middle‐aged patients were admitted to our hospital for an abrupt onset of diabetes, in diabetic ketoacidosis, with a very short duration of hyperglycaemic symptoms. Their clinical course was similar. Case 1 never demonstrated any markers of pancreatic immunogenicity. Case 2 had high levels of decarboxylase glutamic acid autoantibodies (GADAb), before the IFN‐α treatment that persisted. We compared initial β‐cell function and metabolic control with a group of middle‐aged patients from our hospital who had recently been diagnosed with Type 1 diabetes mellitus (DM1). In contrast to these, the onset of the disease was particularly severe with β‐cell function substantially impaired and displaying unstable short‐term metabolic control.

Conclusions  Type 1 diabetes should be considered as a potential complication if IFN is administered to patients with chronic hepatitis C. Its onset may be severe and result in short‐term difficulties in metabolic control.

Diabet. Med. 18, 764–767 (2001)
Insulin infusion normalizes fasting and post‐prandial albumin and fibrinogen synthesis in Type 1 diabetes mellitus
Authors: Bruttomesso D. , Iori E. , Kiwanuka E. , Zanetti M. , Pianta A. , Vettore M. , Tiengo A. , Tessari P.
Published: March 2003

Aims  The effect of metabolic control on hepatic synthesis of plasma proteins in Type 1 diabetes mellitus (T1DM), in the post‐absorptive and post‐prandial state, is not known.

Methods  We measured fractional synthetic rates (FSR) of albumin and fibrinogen in six insulin‐infused T1DM patients and in five to nine control subjects, before and for approx. 4 h after a mixed liquid meal. Phenylalanine tracer precursor/product relationships and steady‐state conditions were used. In the post‐absorptive state, patients were studied in near euglycaemic conditions after an overnight intravenous insulin infusion. During the meal (approx. 11 kcal/kg), the insulin infusion rate was increased to maintain plasma glucose concentrations below approx. 10 mmol/l.

Results  Post‐absorptive FSR of albumin (5.7 ± 0.6%/day) and fibrinogen (11.3 ± 0.6%/day) in T1DM were similar to control values (6.4 ± 0.9 and 13.1 ± 1.1, respectively). After the meal, albumin FSR increased (P = 0.0032 by anova) in both groups (T1DM, to 14.4 ± 2.7%/day; controls, to 18.2 ± 3.7%/day). Fibrinogen FSR also increased (P = 0.0048 by anova) in both the T1DM (to 18.2 ± 2.6) and the control subjects (to 27.3 ± 6.2). There was no difference between T1DM and control subjects in the post‐prandial FSR of both proteins.

Conclusions  Albumin and fibrinogen FSR in T1DM can be maintained within near‐normal ranges by insulin infusion under post‐absorptive and post‐prandial conditions.

Diabet. Med. 18, 915–920 (2001)
Recent advances in treatment of youth with Type 1 diabetes: better care through technology
Authors: Tamborlane W. V. , Bonfig W. , Boland E.
Published: March 2003

While treatment of Type 1 diabetes mellitus (T1DM) in children and adolescents is especially difficult, recent technological advances have provided new therapeutic options to clinicians and patients. The urgency to achieve strict diabetes control and the introduction of new and improved insulin pumps have been accompanied by a marked increase in use of continuous subcutaneous insulin infusion (CSII) therapy in youth with diabetes. Results of clinical outcome studies indicate that CSII provides a safe and effective alternative to multiple daily injection (MDI) therapy, even when employed in a regular clinic setting in a large number of children. The safety and efficacy of CSII is further enhanced by the introduction of lispro and aspart insulin. The sharper peaks and shorter duration of action of these very rapid‐acting insulin analogues provides a means to achieve better control of post‐prandial hyperglycaemia with less late post‐prandial and nocturnal hypoglycaemia. Glargine insulin, a soluble and essentially peakless long‐acting insulin analogue, may provide a better basal insulin for MDI regimens, but there are limited published data with this agent in children with T1DM. A number of systems for pulmonary delivery of insulin are in development and preliminary results of Phase III studies have been promising. Like CSII, inhaled insulin allows the child to take bolus insulin doses before each meal without having to take a premeal injection. A major obstacle to effective treatment is that self‐monitoring of three to four blood glucose levels a day often misses the marked glycaemic excursions that characterize T1DM in young patients. On the other hand, new continuous glucose sensing systems provide a wealth of data that can be used to optimize basal and bolus therapy, regardless of how insulin is administered. Even more important, we may finally be at the threshold of development of a practically applicable artificial pancreas.

Diabet. Med. 18, 864–870 (2001)
Influence of lipoprotein(a) on restenosis after femoropopliteal percutaneous transluminal angioplasty in Type 2 diabetic patients
Authors: Maca T. H. , Ahmadi R. , Derfler K. , Ehringer H. , Gschwandtner M. E. , Hörl W. , Katzenschlager R. , Müller‐Knespel E. , Koppensteiner R. , Schneider B. , Stümpflen A. , Ugurluoglu A. , Minar E.
Published: March 2003

Objective  The influence of vascular morphology and metabolic parameters including lipoprotein(a) (Lp(a)) on restenosis after peripheral angioplasty has been compared in Type 2 diabetes (DM) vs. non‐diabetic patients (ND).

Research design and methods  The clinical course and risk profile of 132 (54 DM vs. 78 ND) patients with peripheral arterial occlusive disease (PAD) were observed prospectively following femoropopliteal angioplasty (PTA). Clinical examination, oscillometry, ankle brachial blood pressure index (ABI) and the toe systolic blood pressure index (TSPI) were used during follow‐up. Duplex sonography and reangiography were also used to verify suspected restenosis or reocclusion.

Results  At the time of intervention patients with DM had a lower median Lp(a) of 9 vs. 15 mg/dl (P < 0.01) in patients without diabetes. Recurrence within 1 year after PTA occurred in 25 diabetic (= 46%, Lp(a) 12 mg/dl) and 30 non‐diabetic (= 38%, Lp(a) 48 mg/dl) patients. DM patients with 1 year’s patency had a median Lp(a) of 7 vs. 11 mg/dl in non‐diabetic patients (P < 0.05). However, 12 months after angioplasty Lp(a) correlated negatively with the ABI (r = –0.44, P < 0.01) in diabetic and in non‐diabetic patients (r = –0.20, P < 0.05). The probability of recurrence after PTA continuously increased with higher levels of Lp(a) in each subgroup of patients.

Conclusions  Our data indicate that Lp(a) is generally lower in those with peripheral arterial occlusive disease and Type 2 diabetes than in non‐diabetic individuals. The increased risk for restenosis with rising levels of Lp(a) is set at a lower Lp(a) in diabetes and may be more harmful for diabetic patients.
Gastric emptying in diabetes: clinical significance and treatment
Authors: Horowitz M. , O’Donovan D. , Jones K. L. , Feinle C. , Rayner C. K. , Samsom M.
Published: March 2003

The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30–50% of outpatients with long‐standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post‐prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post‐prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.
Insulin, insulin propeptides and intima‐media thickness in the carotid artery in 58‐year‐old clinically healthy men. The Atherosclerosis and Insulin Resistance study (AIR)
Authors: Bokemark L. , Wikstrand J. , Wedel H. , Fagerberg B.
Published: March 2003

Aims To examine the relationship between specific (intact) insulin, insulin propeptides and subclinical atherosclerosis.

Methods A cross‐sectional study based on a stratified sampling of randomly selected, clinically healthy 58‐year‐old men (n = 391). Ultrasound examinations of the carotid arteries were performed with measurement of intima‐media thickness (IMT) in the common carotid artery and in the carotid artery bulb. Fasting, cross‐reacting plasma insulin (RIA), specific (intact) insulin, proinsulin, 32,33 split proinsulin and C‐peptide were measured.

Results Plasma concentrations of cross‐reacting plasma insulin, specific insulin, proinsulin, 32,33 split proinsulin and C‐peptide were univariately associated with common carotid artery IMT. Established risk factors such as blood pressure, smoking, apoB, triglycerides, body mass index (BMI), and waist–hip ratio were also related to IMT. After adjustment for smoking, apoB, blood pressure and triglycerides, cross‐reacting plasma insulin, proinsulin and C‐peptide but not specific insulin and split 32,33 proinsulin remained associated with carotid artery IMT. No associations remained after adjustment for BMI.

Conclusions Fasting plasma proinsulin, C‐peptide, and insulin by cross‐reacting RIA was associated with common carotid artery IMT independent of several conventional risk factors for atherosclerosis. The multicollinearity between the insulin peptides and propeptides makes it difficult to clarify the exact role of each peptide.
Is coeliac disease more prevalent in young adults with coexisting Type 1 diabetes mellitus and autoimmune thyroid disease compared with those with Type 1 diabetes mellitus alone?
Authors: Li Voon Chong J. S. W. , Leong K. S. , Wallymahmed M. , Sturgess R. , MacFarlane I. A.
Published: March 2003

Aim It is known that patients with Type 1 diabetes mellitus are more prone to develop coeliac disease and that autoimmune thyroid disease occurs more frequently in patients with coeliac disease. We therefore assessed whether coeliac disease, either known or occult, occurs more frequently in young/middle aged adults with Type 1 diabetes and coexisting autoimmune thyroid dysfunction than in adults with Type 1 diabetes alone.

Methods The prevalence of known coeliac disease was assessed in 509 (301 males, aged 16–55 years) patients with Type 1 diabetes, 28 (5.5%) of whom had treated autoimmune thyroid disease. In a second study 38 patients with Type 1 diabetes and coexisting autoimmune thyroid disease along with 112 patients with Type 1 diabetes alone were then screened for coeliac disease using serum IgA endomysial antibodies and IgA gliadin antibodies.

Results Seven of the 509 patients (1.4%) had been diagnosed with coeliac disease and two of these had later developed autoimmune thyroid disease (both hypothyroid). The subsequent screening exercise found that one of the 38 patients with both Type 1 diabetes and thyroid disease had positive endomysial antibodies on screening. However, duodenal biopsy was negative for coeliac disease. There were two patients with positive endomysial antibodies in the group of 112 patients with diabetes only. Both had duodenal biopsy but only one was consistent with coeliac disease.

Conclusion The prevalence of known coeliac disease in this young adult Type 1 diabetes clinic in North‐west England was 7/509 (1.4%). Two of these seven patients with coeliac disease were from the group of 28 who had autoimmune thyroid disease as well. Therefore we suggest that patients with known coeliac disease and Type 1 diabetes should be screened for autoimmune thyroid disease. The second screening study then found 3/150 (2%) to have a serological marker for coeliac disease. However, patients with both Type 1 diabetes and autoimmune thyroid disease were not more likely to have occult coeliac disease compared with those with Type 1 diabetes only.
Neuropsychological functioning in older people with Type 2 diabetes: the effect of controlling for confounding factors
Authors: Asimakopoulou K. G. , Hampson S. E. , Morrish N. J.
Published: March 2003

Aims and methods Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 ± 9.62 years) people with Type 2 diabetes (Group 1) and 33 non‐diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2).

Results Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people’s verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self‐reported memory problems.

Conclusions These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.
Transforming growth factor‐beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers
Authors: Jude E. B. , Blakytny R. , Bulmer J. , Boulton A. J. M. , Ferguson M. W. J.
Published: March 2003

Aims To study the distribution of transforming growth factor‐beta (TGF‐β) 1, 2 and 3, and TGF‐β receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF‐βs with those of chronic venous ulcers.

Methods Skin biopsies were obtained from the leg or the foot of non‐diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF‐β 1, 2 and 3 and TGF‐β receptors (RI and RII) was done by staining 8‐µm skin sections using appropriate antibodies. Protein levels of TGF‐β were measured by Western blot analysis.

Results TGF‐β3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF‐β1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers.

Conclusion The lack of TGF‐β1 up‐regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity.
Congenital anomalies in the offspring of women with Type 1, Type 2 and gestational diabetes
Authors: Farrell T. , Neale L. , Cundy T.
Published: March 2003

Aim To determine the frequency of major congenital anomalies in the offspring of women with gestational diabetes (GDM), classified according to their postpartum glucose tolerance status.

Methods A prospective study of pregnancies in women with Type 1 diabetes (n = 221), Type 2 diabetes (n = 317) and GDM (n = 1822) between 1985 and 2000 (15 years). Congenital anomalies were detected by antenatal ultrasound or postnatal examination.

Results The frequency of major congenital anomalies in the offspring was 5.9% (95% confidence interval (CI) 3.2–9.8) for women with Type 1 diabetes; 4.4% (95% CI 2.4–7.3) for women with Type 2 diabetes; and 1.4% (95% CI 0.9–2.0) for women with GDM. Two hundred and thirty‐seven women with GDM (13%) had diabetes diagnosed on early (6‐week) postpartum glucose tolerance testing. The frequency of major congenital anomalies in their offspring was 4.6% (95% CI 2.3–8.2), compared with 0.9% (95% CI 0.5–1.5) for the remainder of the GDM group (P < 0.0001).

Conclusions GDM is not a homogeneous group with regard to the risk of major congenital anomalies. In those with diabetes on early postpartum testing, who are likely to have had unrecognized Type 2 diabetes antedating their pregnancy, the rate of major congenital anomalies is the same as for women with established Type 1 or Type 2 diabetes. In the remainder of the GDM group, the rate does not differ from the non‐diabetic background rate.
Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle‐aged men
Authors: Laaksonen D. E. , Lakka T. A. , Lakka H.‐M. , Nyyssönen K. , Rissanen T. , Niskanen L. K. , Salonen J. T.
Published: March 2003

Aims Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM.

Methods Middle‐aged normoglycaemic men (n = 895) participating in a prospective cohort study were followed up after 4 years.

Results At baseline proportions of serum esterified and non‐esterified saturated fatty acids were increased and polyunsaturated fatty acids decreased in men who after 4 years had developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid composition as recorded in 4‐day dietary records were noted. In logistic regression analyses adjusting for age; obesity; and fasting lipid, glucose and insulin concentrations, men with proportions of non‐esterified and esterified linoleate in the upper third had nearly half the risk for IFG or DM compared with the lower third. In covariate analyses, baseline non‐esterified linoleate proportions were associated with changes in fasting insulin and glucose concentrations over the 4‐year follow‐up. Baseline esterified fatty acid composition was also associated with changes in insulin.

Conclusions High serum linoleate proportions decreased the risk of developing IFG or DM in middle‐aged men over a 4‐year follow‐up, possibly mediated in part by insulin resistance. These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism.
Congenital anomalies and first life year surveillance in Type 1 diabetic births
Authors: Vääräsmäki M. , Gissler M. , Ritvanen A. , Hartikainen A.‐L.
Published: March 2003

Aims To evaluate the rate of congenital anomalies (CA) and the reasons for mortality from 22 weeks of gestation until 1 year of age in births by Type 1 diabetic mothers.

Methods Population‐based cohort study using combined data from four national health registers in Finland during 1991–1995, including 954 singleton pregnancies complicated by Type 1 diabetes.

Results Sixty births (629/10 000) involved registered major CA, of which 68% (n = 41) were isolated and 22% (n = 13) multiple anomalies, and in six cases, a syndrome was diagnosed (10%). After the exclusion of syndromes, the total number of anomalies was 73. Of the malformed infants, 63% were boys. The total rate of deaths among births until 1 year of age was higher in diabetic than in non‐diabetic mothers (19.9/1000 vs. 8.1/1000): especially the rates of stillborns (odds ratio 2.4; 95% confidence interval 1.2–4.7) and post‐neonatal deaths (3.8; 1.6–9.2) were higher. Of perinatal mortality (PNM) from the 22nd gestational week to the age of 7 days (13.6/1000), 23% were due to CA, 23% to prematurity, and the rest were intrauterine, mostly unexplained, deaths. Respiratory distress syndrome was the main cause of death among infants.

Conclusions The rate of CAs in Type 1 diabetic pregnancies is still high, but their proportion as a cause of PNM has decreased. Though PNM rate was low, post‐neonatal mortality was significantly increased, reflecting the shift of deaths from the perinatal period to a later age.
Neuropeptides and appetite control
Authors: Wilding J. P. H.
Published: March 2003

Obesity is important in the aetiology of type 2 diabetes, and presents a major barrier to its successful prevention and management. Obesity develops when energy intake exceeds energy expenditure over time. A complex system has evolved to maintain energy homeostasis, but this is biased towards weight gain. Meal size is controlled by a series of short‐term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin whereas others may initiate meals, such as the recently discovered hormone, ghrelin. Other hormones such as insulin and leptin, together with circulating nutrients, indicate long‐term energy stores. All these signals act at several central nervous system (CNS) sites but the pathways converge on the hypothalamus, which contains a large number of peptide and other neurotransmitters that influence food intake. As energy deficit is most likely to compromise survival, it is not surprising that the most powerful of these pathways are those that increase food intake and decrease energy expenditure when stores are depleted. When energy stores are low, production of leptin from adipose tissue, and thus circulating leptin concentrations fall, leading to increased production of hypothalamic neurotransmitters that strongly increase food intake, such as neuropeptide Y (NPY), galanin and agouti‐related protein (AGRP) and decreased levels of α‐melanocyte‐stimulating hormone (α‐MSH), cocaine and amphetamine‐regulated transcript (CART) and neurotensin that reduce food intake and increase energy expenditure. The finding that mutations in leptin and POMC lead to severe early onset obesity in bumans has highlighted the importance of these peptides in humans. This new understanding may eventually lead to new treatments for obesity that will be of particular benefit in the prevention and treatment of type 2 diabetes.

Diabet. Med. 19, 619–627 (2002)
Ultrasonography of plantar soft tissues thickness in young people with diabetes
Authors: Duffin A. C. , Lam A. , Kidd R. , Chan A. K. F. , Donaghue K. C.
Published: March 2003

Aims The aims of this study were to examine soft tissue changes in the skin and plantar aponeurosis of young people with Type 1 diabetes mellitus (T1DM) and to evaluate any relationship between any soft tissue changes, arch length, limited joint mobility (LJM) and plantar pressure.

Methods The thickness of the skin on the plantar surface of the foot and plantar aponeurosis were examined using ultrasound in 216 young people with diabetes and 57 controls. Foot length, arch length, joint mobility, peak pressure and pressure time integrals were evaluated.

Results Skin was not significantly thicker in the diabetic subjects. The plantar aponeurosis was significantly thicker in the diabetic subjects and was associated with foot size, male gender and subtalar joint (ST) LJM (P < 0.01). Males were nearly three times more likely to have thickened plantar aponeurosis.

Conclusion Soft tissue thickening in young people with T1DM affects the deeper structures on the plantar surface of the foot rather than the skin. Thickening of the plantar aponeurosis was associated with LJM at the ST joint and male gender, but was not associated with plantar pressure or arch height changes. Plantar aponeurosis thickening does not appear to alter foot mechanics in young people with T1DM.

Diabet. Med 19, 1009–1013 (2002)
The role of the growth hormone–insulin‐like growth factor axis in glucose homeostasis
Authors: Holt R. I. G. , Simpson H. L. , Sönksen P. H.
Published: March 2003

Homeostatic mechanisms normally maintain the plasma glucose concentration within narrow limits despite major fluctuations in supply and demand. There is increasing evidence that the growth hormone (GH)–insulin‐like growth factor (IGF) axis may play an important role in glucose metabolism. GH has potent effects on intermediary metabolism, some of which antagonize the actions of insulin. In contrast, IGF‐I has insulin‐like actions, which are, in the case of glucose metabolism, opposite to those of GH. There is often deranged glucose metabolism in situations where GH is deficient or in excess. The clinical administration of GH or IGF‐I results in altered glucose metabolism and changes in insulin resistance. Despite these observations, the precise role of GH and IGF‐I and their interactions with insulin in controlling normal glucose homeostasis are unknown. In diabetes, GH secretion is abnormally increased as a result of reduced portal insulin resulting in impaired hepatic IGF‐I generation. Evidence suggests that this may contribute to the development of diabetic microvascular complications. IGF‐I ‘replacement’ in diabetes is under investigation and new methods of delivering IGF‐I as a complex with IGFBP‐3 offer exciting new prospects.

Diabet. Med. 20, 3–15 (2003)
Foot complications in Type 2 diabetes: an Australian population‐based study
Authors: Tapp R. J. , Shaw J. E. , De Courten M. P. , Dunstan D. W. , Welborn T. A. , Zimmet P. Z.
Published: March 2003

Aims  To determine the prevalence and risk factors for neuropathy and peripheral vascular disease (PVD) in the Australian diabetic population and identify those at high risk of foot ulceration.

Methods  The Australian Diabetes Obesity and Lifestyle study included 11 247 adults aged ≥ 25 years in 42 randomly selected areas of Australia. Neuropathy and PVD were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance (total n = 2436).

Results  The prevalence of peripheral neuropathy was 13.1% in those with known diabetes (KDM) and 7.1% in those with newly diagnosed (NDM). The prevalence of PVD was 13.9% in KDM and 6.9% in NDM. Of those with diabetes, 19.6% were at risk of foot ulceration. Independent risk factors for peripheral neuropathy were diabetes duration (odds ratio (95% CI) 1.73 (1.33–2.28) per 10 years), height (1.42 (1.08–1.88) per 10 cm), age (2.57 (1.94–3.40) per 10 years) and uric acid (1.59 (1.21–2.09) per 0.1 mmol/l). Risk factors for PVD were diabetes duration (1.64 (1.25–2.16) per 10 years), age (2.45 (1.86–3.22) per 10 years), smoking (2.07 (1.00–4.28)), uric acid (1.03 (1.00–1.06) per 0.1 mmol/l) and urinary albumin/creatinine ratio (1.11 (1.01–1.21) per 1 mg/mmol).

Conclusions  The prevalence of neuropathy and PVD was lower in this population than has been reported in other populations. This may reflect differences in sampling methods between community and hospital‐based populations. Nevertheless, a substantial proportion of the diabetic population had risk factors for foot ulceration.
Comparison of patients’ and healthcare professionals’ beliefs about and attitudes towards Type 2 diabetes
Authors: Clark M. , Hampson S. E.
Published: March 2003

Aims  To compare patients’ and healthcare professionals’ beliefs and attitudes towards diabetes.

Methods  One hundred and four healthcare professionals (nurses, dieticians, general practitioners) and 100 of their patients with Type 2 diabetes completed the Diabetes Attitude Scale, 3rd version (DAS‐3). Healthcare professionals also answered questions about their provision of diabetes care.

Results  Healthcare professionals viewed Type 2 diabetes as more serious than their patients. Most of the healthcare professionals considered diabetes harder to treat than other chronic conditions and felt that they did not have adequate time and resources to treat their diabetes patients effectively.

Conclusions  This study suggests that an important part of forming collaborative alliances with patients is to recognize the distinction between practitioner and patient perspectives in Type 2 diabetes.
Distribution and habitat use of water frog hybrid complexes in France
Authors: Pagano Alain , Crochet Pierre André , Graf J.‐D. , Joly Pierre , Lodé Thierry
Published: March 2003

Hybrid zones are either distributed along clines or in a mosaic of patches. This distribution may depend upon variation in taxon habitat use. Habitat use and distribution of diverse taxa of water frogs (Rana ridibunda,R. lessonae,R. perezi,R.kl.grafiandR.kl.esculenta) in France are analysed to determine whether water frog complexes conform to the mosaic or clinal model. Biogeographical scenarios may be invoked in order to explain the distribution of water frogs. However, the distribution ofR. pereziandR.kl.grafi, being restricted to regions characterized by Mediterranean or Oceanic climatic conditions, suggests that these frogs do not endure cold winters.R. ridibundais widespread in Southern France and its distribution suggests multiple introductions. It is concluded that water frogs conform to the mosaic zone model rather than to the tension zone model because: (i) taxa exhibited differences in habitat use, (ii) pure parental species were documented and (iii) hybrids are not unfit relative to parental species.